Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid<xref ref-type="fn" rid="fn2">▿</xref> <xref ref-type="fn" rid="fn1">†</xref> </title><author><name sortKey="Holodniy, Mark" sort="Holodniy, Mark" uniqKey="Holodniy M" first="Mark" last="Holodniy">Mark Holodniy</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Penzak, Scott R" sort="Penzak, Scott R" uniqKey="Penzak S" first="Scott R." last="Penzak">Scott R. Penzak</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Straight, Timothy M" sort="Straight, Timothy M" uniqKey="Straight T" first="Timothy M." last="Straight">Timothy M. Straight</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Davey, Richard T" sort="Davey, Richard T" uniqKey="Davey R" first="Richard T." last="Davey">Richard T. Davey</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lee, Kelvin K" sort="Lee, Kelvin K" uniqKey="Lee K" first="Kelvin K." last="Lee">Kelvin K. Lee</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Goetz, Matthew Bidwell" sort="Goetz, Matthew Bidwell" uniqKey="Goetz M" first="Matthew Bidwell" last="Goetz">Matthew Bidwell Goetz</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Raisch, Dennis W" sort="Raisch, Dennis W" uniqKey="Raisch D" first="Dennis W." last="Raisch">Dennis W. Raisch</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Cunningham, Francesca" sort="Cunningham, Francesca" uniqKey="Cunningham F" first="Francesca" last="Cunningham">Francesca Cunningham</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lin, Emil T" sort="Lin, Emil T" uniqKey="Lin E" first="Emil T." last="Lin">Emil T. Lin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Olivo, Noemi" sort="Olivo, Noemi" uniqKey="Olivo N" first="Noemi" last="Olivo">Noemi Olivo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Deyton, Lawrence R" sort="Deyton, Lawrence R" uniqKey="Deyton L" first="Lawrence R." last="Deyton">Lawrence R. Deyton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18559644</idno><idno type="pmc">2533494</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533494</idno><idno type="RBID">PMC:2533494</idno><idno type="doi">10.1128/AAC.00047-08</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000324</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000324</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid<xref ref-type="fn" rid="fn2">▿</xref> <xref ref-type="fn" rid="fn1">†</xref> </title><author><name sortKey="Holodniy, Mark" sort="Holodniy, Mark" uniqKey="Holodniy M" first="Mark" last="Holodniy">Mark Holodniy</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Penzak, Scott R" sort="Penzak, Scott R" uniqKey="Penzak S" first="Scott R." last="Penzak">Scott R. Penzak</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Straight, Timothy M" sort="Straight, Timothy M" uniqKey="Straight T" first="Timothy M." last="Straight">Timothy M. Straight</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Davey, Richard T" sort="Davey, Richard T" uniqKey="Davey R" first="Richard T." last="Davey">Richard T. Davey</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lee, Kelvin K" sort="Lee, Kelvin K" uniqKey="Lee K" first="Kelvin K." last="Lee">Kelvin K. Lee</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Goetz, Matthew Bidwell" sort="Goetz, Matthew Bidwell" uniqKey="Goetz M" first="Matthew Bidwell" last="Goetz">Matthew Bidwell Goetz</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Raisch, Dennis W" sort="Raisch, Dennis W" uniqKey="Raisch D" first="Dennis W." last="Raisch">Dennis W. Raisch</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Cunningham, Francesca" sort="Cunningham, Francesca" uniqKey="Cunningham F" first="Francesca" last="Cunningham">Francesca Cunningham</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Lin, Emil T" sort="Lin, Emil T" uniqKey="Lin E" first="Emil T." last="Lin">Emil T. Lin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Olivo, Noemi" sort="Olivo, Noemi" uniqKey="Olivo N" first="Noemi" last="Olivo">Noemi Olivo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Deyton, Lawrence R" sort="Deyton, Lawrence R" uniqKey="Deyton L" first="Lawrence R." last="Deyton">Lawrence R. Deyton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Antimicrobial Agents and Chemotherapy</title><idno type="ISSN">0066-4804</idno><idno type="eISSN">1098-6596</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections. In the event of an influenza pandemic, oseltamivir supplies may be limited; thus, alternative dosing strategies for oseltamivir prophylaxis should be explored. Healthy volunteers were randomized to a three-arm, open-label study and given 75 mg oral oseltamivir every 24 h (group 1), 75 mg oseltamivir every 48 h (q48h) combined with 500 mg probenecid four times a day (group 2), or 75 mg oseltamivir q48h combined with 500 mg probenecid twice a day (group 3) for 15 days. Pharmacokinetic data, obtained by noncompartmental methods, and safety data are reported. Forty-eight subjects completed the pharmacokinetic analysis. The study drugs were generally well tolerated, except for one case of reversible grade 4 thrombocytopenia in a subject in group 2. The calculated 90% confidence intervals (CIs) for the geometric mean ratios between groups 2 and 3 and group 1 were outside the bioequivalence criteria boundary (0.80 to 1.25) at 0.63 to 0.89 for group 2 versus group 1 and 0.57 to 0.90 for group 3 versus group 1. The steady-state apparent oral clearance of oseltamivir carboxylate was significantly less in groups 2 (7.4 liters/h; 90% CI, 6.08 to 8.71) and 3 (7.19 liters/h; 90% CI, 6.41 to 7.98) than in group 1 (9.75 liters/h; 90% CI, 6.91 to 12.60) (<italic>P</italic> < 0.05 for both comparisons by analysis of variance). The (arithmetic) mean concentration at 48 h for group 2 was not significantly different from the mean concentration at 24 h for group 1 (42 ± 76 and 81 ± 54 ng/ml, respectively; <italic>P</italic> = 0.194), but the mean concentration at 48 h for group 3 was significantly less than the mean concentration at 24 h for group 1 (23 ± 26 and 81 ± 54 ng/ml, respectively; <italic>P</italic> = 0.012). Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Antimicrob Agents Chemother</journal-id><journal-id journal-id-type="publisher-id">aac</journal-id><journal-title>Antimicrobial Agents and Chemotherapy</journal-title><issn pub-type="ppub">0066-4804</issn><issn pub-type="epub">1098-6596</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18559644</article-id><article-id pub-id-type="pmc">2533494</article-id><article-id pub-id-type="publisher-id">0047-08</article-id><article-id pub-id-type="doi">10.1128/AAC.00047-08</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject></subj-group></article-categories><title-group><article-title>Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid<xref ref-type="fn" rid="fn2">▿</xref> <xref ref-type="fn" rid="fn1">†</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Holodniy</surname><given-names>Mark</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="aff" rid="aff1">3</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Penzak</surname><given-names>Scott R.</given-names></name><xref ref-type="aff" rid="aff1">4</xref></contrib><contrib contrib-type="author"><name><surname>Straight</surname><given-names>Timothy M.</given-names></name><xref ref-type="aff" rid="aff1">5</xref></contrib><contrib contrib-type="author"><name><surname>Davey</surname><given-names>Richard T.</given-names></name><xref ref-type="aff" rid="aff1">6</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Kelvin K.</given-names></name><xref ref-type="aff" rid="aff1">3</xref><xref ref-type="aff" rid="aff1">7</xref></contrib><contrib contrib-type="author"><name><surname>Goetz</surname><given-names>Matthew Bidwell</given-names></name><xref ref-type="aff" rid="aff1">8</xref><xref ref-type="aff" rid="aff1">9</xref></contrib><contrib contrib-type="author"><name><surname>Raisch</surname><given-names>Dennis W.</given-names></name><xref ref-type="aff" rid="aff1">10</xref></contrib><contrib contrib-type="author"><name><surname>Cunningham</surname><given-names>Francesca</given-names></name><xref ref-type="aff" rid="aff1">11</xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Emil T.</given-names></name><xref ref-type="aff" rid="aff1">12</xref></contrib><contrib contrib-type="author"><name><surname>Olivo</surname><given-names>Noemi</given-names></name><xref ref-type="aff" rid="aff1">3</xref></contrib><contrib contrib-type="author"><name><surname>Deyton</surname><given-names>Lawrence R.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">13</xref></contrib></contrib-group><aff id="aff1">Office of Public Health and Environmental Hazards, U.S. Department of Veterans Affairs, Washington, DC,<label>1</label> Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California,<label>2</label> VA Palo Alto Health Care System, Palo Alto, California,<label>3</label> Clinical Pharmacokinetics Research Laboratory, National Institutes of Health, Bethesda, Maryland,<label>4</label> Department of Clinical Investigation, Brooke Army Medical Center, Ft. Sam Houston, Texas,<label>5</label> CRS/LIR/NIAID, National Institutes of Health, Bethesda, Maryland,<label>6</label> VA Cooperative Studies Program Coordinating Center, Palo Alto, California,<label>7</label> Greater Los Angeles Health Care System, Los Angeles, California,<label>8</label> Infectious Diseases Section, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California,<label>9</label> VA Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico,<label>10</label> Pharmacy Benefits Management Group, U.S. Department of Veterans Affairs, Hines, Illinois,<label>11</label> Department of Biopharmaceutical Sciences, UCSF, San Francisco, California,<label>12</label> George Washington University School of Medicine and Health Sciences, Washington, DC<label>13</label></aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Public Health Research Center, VA Palo Alto Health Care System, 3801 Miranda Ave. (132), Palo Alto, CA 94304. Phone: (650) 852-3408. Fax: (650) 858-3978. E-mail: <email>Holodniy@stanford.edu</email></p></fn></author-notes><pub-date pub-type="ppub"><month>9</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>16</day><month>6</month><year>2008</year></pub-date><volume>52</volume><issue>9</issue><fpage>3013</fpage><lpage>3021</lpage><history><date date-type="received"><day>14</day><month>1</month><year>2008</year></date><date date-type="rev-recd"><day>25</day><month>4</month><year>2008</year></date><date date-type="accepted"><day>6</day><month>6</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2008, American Society for Microbiology</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:href="zac00908003013.pdf"></self-uri><abstract><p>Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections. In the event of an influenza pandemic, oseltamivir supplies may be limited; thus, alternative dosing strategies for oseltamivir prophylaxis should be explored. Healthy volunteers were randomized to a three-arm, open-label study and given 75 mg oral oseltamivir every 24 h (group 1), 75 mg oseltamivir every 48 h (q48h) combined with 500 mg probenecid four times a day (group 2), or 75 mg oseltamivir q48h combined with 500 mg probenecid twice a day (group 3) for 15 days. Pharmacokinetic data, obtained by noncompartmental methods, and safety data are reported. Forty-eight subjects completed the pharmacokinetic analysis. The study drugs were generally well tolerated, except for one case of reversible grade 4 thrombocytopenia in a subject in group 2. The calculated 90% confidence intervals (CIs) for the geometric mean ratios between groups 2 and 3 and group 1 were outside the bioequivalence criteria boundary (0.80 to 1.25) at 0.63 to 0.89 for group 2 versus group 1 and 0.57 to 0.90 for group 3 versus group 1. The steady-state apparent oral clearance of oseltamivir carboxylate was significantly less in groups 2 (7.4 liters/h; 90% CI, 6.08 to 8.71) and 3 (7.19 liters/h; 90% CI, 6.41 to 7.98) than in group 1 (9.75 liters/h; 90% CI, 6.91 to 12.60) (<italic>P</italic> < 0.05 for both comparisons by analysis of variance). The (arithmetic) mean concentration at 48 h for group 2 was not significantly different from the mean concentration at 24 h for group 1 (42 ± 76 and 81 ± 54 ng/ml, respectively; <italic>P</italic> = 0.194), but the mean concentration at 48 h for group 3 was significantly less than the mean concentration at 24 h for group 1 (23 ± 26 and 81 ± 54 ng/ml, respectively; <italic>P</italic> = 0.012). Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Mean plasma oseltamivir concentrations (± standard error of the mean) versus time in 18 subjects receiving oseltamivir 75 mg daily for 2 weeks.</p></caption><graphic xlink:href="zac0090875000001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>Mean plasma probenecid concentrations (± standard error of the mean) versus time in subjects receiving probenecid 500 mg QID for 2 weeks (group 2; open diamonds) and 500 mg BID for 2 weeks (group 3; closed squares).</p></caption><graphic xlink:href="zac0090875000002"></graphic></fig><fig position="float" id="f3"><label>FIG. 3.</label><caption><p>Mean plasma oseltamivir carboxylate concentrations (± standard error of the mean) versus time in three groups of healthy human subjects after 2 weeks of oseltamivir administration. Group 1 (solid diamonds, dashed line) received oseltamivir 75 mg q24h; group 2 (solid squares, solid line) received oseltamivir 75 mg q48h plus probenecid 500 mg QID; and group 3 (open triangles, solid line) received oseltamivir 75 mg q48h plus probenecid 500 mg BID. Error bars indicate standard errors of the means.</p></caption><graphic xlink:href="zac0090875000003"></graphic></fig><table-wrap position="float" id="t1"><label>TABLE 1.</label><caption><p>Baseline subject demographics and physical characteristics by treatment group</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Characteristic</th><th colspan="1" rowspan="1" align="center" valign="bottom">Group 1</th><th colspan="1" rowspan="1" align="center" valign="bottom">Group 2</th><th colspan="1" rowspan="1" align="center" valign="bottom">Group 3</th><th colspan="1" rowspan="1" align="center" valign="bottom">Total</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>P</italic> value</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">No. of subjects randomized</td><td colspan="1" rowspan="1" align="center" valign="top">18</td><td colspan="1" rowspan="1" align="center" valign="top">19</td><td colspan="1" rowspan="1" align="center" valign="top">16</td><td colspan="1" rowspan="1" align="center" valign="top">53</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Age</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Mean (SD)</td><td colspan="1" rowspan="1" align="center" valign="top">55.6 (13.6)</td><td colspan="1" rowspan="1" align="center" valign="top">54.1 (18.5)</td><td colspan="1" rowspan="1" align="center" valign="top">52.4 (19.2)</td><td colspan="1" rowspan="1" align="center" valign="top">54.1 (16.9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.8706</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Median</td><td colspan="1" rowspan="1" align="center" valign="top">56.5</td><td colspan="1" rowspan="1" align="center" valign="top">62</td><td colspan="1" rowspan="1" align="center" valign="top">55.5</td><td colspan="1" rowspan="1" align="center" valign="top">56</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Range</td><td colspan="1" rowspan="1" align="center" valign="top">28-75</td><td colspan="1" rowspan="1" align="center" valign="top">23-79</td><td colspan="1" rowspan="1" align="center" valign="top">22-76</td><td colspan="1" rowspan="1" align="center" valign="top">22-79</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Sex (no. [%] of randomized subjects)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Male</td><td colspan="1" rowspan="1" align="center" valign="top">10 (56)</td><td colspan="1" rowspan="1" align="center" valign="top">11 (58)</td><td colspan="1" rowspan="1" align="center" valign="top">10 (63)</td><td colspan="1" rowspan="1" align="center" valign="top">31 (58)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.9173</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Female</td><td colspan="1" rowspan="1" align="center" valign="top">8 (44)</td><td colspan="1" rowspan="1" align="center" valign="top">8 (42)</td><td colspan="1" rowspan="1" align="center" valign="top">6 (38)</td><td colspan="1" rowspan="1" align="center" valign="top">22 (42)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Race (no. [%] of randomized subjects)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> White</td><td colspan="1" rowspan="1" align="center" valign="top">13 (72)</td><td colspan="1" rowspan="1" align="center" valign="top">12 (63)</td><td colspan="1" rowspan="1" align="center" valign="top">15 (94)</td><td colspan="1" rowspan="1" align="center" valign="top">40 (75)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.6357</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Black</td><td colspan="1" rowspan="1" align="center" valign="top">2 (11)</td><td colspan="1" rowspan="1" align="center" valign="top">3 (16)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">5 (9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Hispanic</td><td colspan="1" rowspan="1" align="center" valign="top">1 (6)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (5)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">2 (4)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Asian/Pacific Islander</td><td colspan="1" rowspan="1" align="center" valign="top">1 (6)</td><td colspan="1" rowspan="1" align="center" valign="top">2 (11)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">3 (6)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> American</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Indian/Alaskan</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Multiple races</td><td colspan="1" rowspan="1" align="center" valign="top">1 (6)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (5)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (6)</td><td colspan="1" rowspan="1" align="center" valign="top">3 (6)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Unknown</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="center" valign="top">0 (0)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Ht (in.)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Mean (SD)</td><td colspan="1" rowspan="1" align="center" valign="top">67.9 (3.4)</td><td colspan="1" rowspan="1" align="center" valign="top">68 (3.7)</td><td colspan="1" rowspan="1" align="center" valign="top">67.1 (4)</td><td colspan="1" rowspan="1" align="center" valign="top">67.7 (3.6)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.7459</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Median</td><td colspan="1" rowspan="1" align="center" valign="top">67.5</td><td colspan="1" rowspan="1" align="center" valign="top">68</td><td colspan="1" rowspan="1" align="center" valign="top">67.8</td><td colspan="1" rowspan="1" align="center" valign="top">8</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Range</td><td colspan="1" rowspan="1" align="center" valign="top">63-72</td><td colspan="1" rowspan="1" align="center" valign="top">59-73</td><td colspan="1" rowspan="1" align="center" valign="top">59-72</td><td colspan="1" rowspan="1" align="center" valign="top">59-73</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Wt (lb)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Mean (SD)</td><td colspan="1" rowspan="1" align="center" valign="top">175.8 (41.8)</td><td colspan="1" rowspan="1" align="center" valign="top">176.6 (29.4)</td><td colspan="1" rowspan="1" align="center" valign="top">173 (36.1)</td><td colspan="1" rowspan="1" align="center" valign="top">175.3 (35.3)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.9553</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Median</td><td colspan="1" rowspan="1" align="center" valign="top">176.1</td><td colspan="1" rowspan="1" align="center" valign="top">175.7</td><td colspan="1" rowspan="1" align="center" valign="top">179.3</td><td colspan="1" rowspan="1" align="center" valign="top">176.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Range</td><td colspan="1" rowspan="1" align="center" valign="top">116.8-270.4</td><td colspan="1" rowspan="1" align="center" valign="top">124.4-256.8</td><td colspan="1" rowspan="1" align="center" valign="top">120.8-228.7</td><td colspan="1" rowspan="1" align="center" valign="top">116.8-270.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Body mass index (kg/m<sup>2</sup>)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Mean (SD)</td><td colspan="1" rowspan="1" align="center" valign="top">26.6 (4.9)</td><td colspan="1" rowspan="1" align="center" valign="top">26.8 (3.7)</td><td colspan="1" rowspan="1" align="center" valign="top">26.8 (3.8)</td><td colspan="1" rowspan="1" align="center" valign="top">26.7 (4.1)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.9825</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Median</td><td colspan="1" rowspan="1" align="center" valign="top">26.6</td><td colspan="1" rowspan="1" align="center" valign="top">27</td><td colspan="1" rowspan="1" align="center" valign="top">26.3</td><td colspan="1" rowspan="1" align="center" valign="top">26.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Range</td><td colspan="1" rowspan="1" align="center" valign="top">20.3-39.4</td><td colspan="1" rowspan="1" align="center" valign="top">20.2-37.4</td><td colspan="1" rowspan="1" align="center" valign="top">21.3-34.8</td><td colspan="1" rowspan="1" align="center" valign="top">20.2-39.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr></tbody></table></table-wrap><table-wrap position="float" id="t2"><label>TABLE 2.</label><caption><p>Adverse events after randomization and after randomization by attribution</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="middle">Time to randomization and system organ class</th><th colspan="1" rowspan="2" align="center" valign="middle">Preferred term</th><th colspan="1" rowspan="2" align="center" valign="middle">Severity level</th><th colspan="4" rowspan="1" align="center" valign="bottom">No. of events (no. of subjects)
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Group 1</th><th colspan="1" rowspan="1" align="center" valign="bottom">Group 2</th><th colspan="1" rowspan="1" align="center" valign="bottom">Group 3</th><th colspan="1" rowspan="1" align="center" valign="bottom">Total</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">After randomization</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Blood and lymphatic system disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Thrombocytopenia</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Gastrointestinal disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Constipation</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Flatulence</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Nausea</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">4 (3)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Vomiting</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">2 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="2" align="left" valign="top"> General disorders and administration site conditions</td><td colspan="1" rowspan="1" align="left" valign="top">Chest pain</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Fever</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Infections and infestations</td><td colspan="1" rowspan="1" align="left" valign="top">Upper respiratory infection</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Investigations</td><td colspan="1" rowspan="1" align="left" valign="top">Creatinine level increase</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Elevated liver enzyme levels</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Urinalysis abnormal</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Leukocyte level decrease</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Metabolism and nutrition disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Hyperkalemia</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Musculoskeletal and connective tissue disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Neck pain</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Renal and urinary disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Hematuria</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">3 (2)</td><td colspan="1" rowspan="1" align="center" valign="top">2 (2)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Microscopic hematuria</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">4 (2)</td><td colspan="1" rowspan="1" align="center" valign="top">5 (2)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Proteinuria</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Respiratory, thoracic, and mediastinal disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Runny nose</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Vascular disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Blood pressure fluctuation</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Hypertension</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Hypotension</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Phlebitis</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> After randomization subtotal</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">11 (7)</td><td colspan="1" rowspan="1" align="center" valign="top">22 (10)</td><td colspan="1" rowspan="1" align="center" valign="top">12 (7)</td><td colspan="1" rowspan="1" align="center" valign="top">45 (24)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">After randomization by attribution</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Possibly attributable</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Gastrointestinal disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Constipation</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Flatulence</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Nausea</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">2 (2)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">3 (3)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Vomiting</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="2" align="left" valign="top"> General disorders and administration site conditions</td><td colspan="1" rowspan="1" align="left" valign="top">Chest pain</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Fever</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Investigations</td><td colspan="1" rowspan="1" align="left" valign="top">Creatinine level increase</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Leukocyte level decrease</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">2 (2)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Renal and urinary disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Hematuria</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Microscopic hematuria</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">2 (2)</td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top">4 (4)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Possibly attributable total</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">5</td><td colspan="1" rowspan="1" align="center" valign="top">7</td><td colspan="1" rowspan="1" align="center" valign="top">4</td><td colspan="1" rowspan="1" align="center" valign="top">16 (10)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Positively attributable</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Blood and lymphatic system disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Thrombocytopenia</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">1 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Gastrointestinal disorders</td><td colspan="1" rowspan="1" align="left" valign="top">Nausea</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">2 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">2 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Vomiting</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">2 (1)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">2 (1)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Positively attributable total</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">5 (2)</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">5 (2)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Total</td><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">11 (7)</td><td colspan="1" rowspan="1" align="center" valign="top">22 (10)</td><td colspan="1" rowspan="1" align="center" valign="top">12 (7)</td><td colspan="1" rowspan="1" align="center" valign="top">45 (24)</td></tr></tbody></table></table-wrap><table-wrap position="float" id="t3"><label>TABLE 3.</label><caption><p>Summary of geometric mean pharmacokinetic parameters of oseltamivir carboxylate</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Group</th><th colspan="1" rowspan="1" align="center" valign="bottom">AUC (μg·h/ml)<xref ref-type="table-fn" rid="t3fn1"><italic>a</italic></xref></th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>C</italic><sub>max</sub> (ng/ml)</th><th colspan="1" rowspan="1" align="center" valign="bottom">CL<sub>ss</sub>/<italic>F</italic><xref ref-type="table-fn" rid="t3fn2"><italic>b</italic></xref> (liters/h)</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>t</italic><sub>1/2</sub> (h)</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">9.75 (6.91-12.60)<xref ref-type="table-fn" rid="t3fn3"><italic>c</italic></xref></td><td colspan="1" rowspan="1" align="char" char="." valign="top">394 (287-392)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">15.4 (12.0-18.8)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.6 (7.00-10.2)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.4 (6.08-8.71)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">394 (329-460)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10.3 (8.66-11.9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">9.5 (3.61-15.4)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.19 (6.41-7.98)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">446 (384-507)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10.4 (8.5-12.4)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.73 (6.26-9.21)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"><italic>P</italic><xref ref-type="table-fn" rid="t3fn4"><italic>d</italic></xref> for group 2 vs group 1</td><td colspan="1" rowspan="1" align="center" valign="top">0.14</td><td colspan="1" rowspan="1" align="center" valign="top">0.65</td><td colspan="1" rowspan="1" align="center" valign="top">0.015</td><td colspan="1" rowspan="1" align="center" valign="top">0.51</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"><italic>P</italic> for group 3 vs group 1</td><td colspan="1" rowspan="1" align="center" valign="top">0.12</td><td colspan="1" rowspan="1" align="center" valign="top">0.78</td><td colspan="1" rowspan="1" align="center" valign="top">0.023</td><td colspan="1" rowspan="1" align="center" valign="top">0.97</td></tr></tbody></table><table-wrap-foot><fn id="t3fn1"><label>a</label><p>The AUC<sub>48</sub>s for group 1 were calculated as the steady-state AUC<sub>24</sub>s times 2; the AUC<sub>48</sub>s for groups 2 and 3 were calculated by using <italic>C</italic><sub>0</sub> as <italic>C</italic><sub>48</sub>, as described in the Materials and Methods.</p></fn><fn id="t3fn2"><label>b</label><p>CL<sub>ss</sub>/<italic>F</italic>, steady-state clearance.</p></fn><fn id="t3fn3"><label>c</label><p>Values in parentheses are 90% confidence intervals.</p></fn><fn id="t3fn4"><label>d</label><p><italic>P</italic> values were determined by ANOVA and the Tukey post-hoc test.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t4"><label>TABLE 4.</label><caption><p>Predose and trough oseltamivir carboxylate concentration comparisons</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Group (conc measured)</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean ± SD concn (ng/ml)</th><th colspan="1" rowspan="1" align="center" valign="bottom">No. of subjects with concn <300 ng/ml/total no. of subjects (%)</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>P</italic> value<xref ref-type="table-fn" rid="t4fn1"><italic>a</italic></xref> vs <italic>C</italic><sub>24</sub> for group 1</th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>P</italic> value vs <italic>C</italic><sub>48</sub> for group 1</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 1 (<italic>C</italic><sub>48</sub>, 24-h dose skipped)</td><td colspan="1" rowspan="1" align="center" valign="top">14 ± 16</td><td colspan="1" rowspan="1" align="center" valign="top">6/18 (33)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 1 (<italic>C</italic><sub>24</sub>)</td><td colspan="1" rowspan="1" align="center" valign="top">81 ± 54</td><td colspan="1" rowspan="1" align="center" valign="top">0/18 (0)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 2 (<italic>C</italic><sub>0</sub>, i.e., <italic>C</italic><sub>48</sub>; predose)</td><td colspan="1" rowspan="1" align="center" valign="top">42 ± 76</td><td colspan="1" rowspan="1" align="center" valign="top">1/16 (6)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.124</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.194</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Group 3 (<italic>C</italic><sub>0</sub>, i.e., <italic>C</italic><sub>48</sub>; predose)</td><td colspan="1" rowspan="1" align="center" valign="top">23 ± 26</td><td colspan="1" rowspan="1" align="center" valign="top">2/16 (13)<xref ref-type="table-fn" rid="t4fn2"><italic>b</italic></xref></td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.012</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.841</td></tr></tbody></table><table-wrap-foot><fn id="t4fn1"><label>a</label><p><italic>P</italic> values were determined by ANOVA.</p></fn><fn id="t4fn2"><label>b</label><p>Two subjects had concentrations between 300 and 400 ng/ml.</p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/PandemieGrippaleV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000324 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000324 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= PandemieGrippaleV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.34. |  |