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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients</title><author><name sortKey="Alobaid, Abdulaziz S" sort="Alobaid, Abdulaziz S" uniqKey="Alobaid A" first="Abdulaziz S." last="Alobaid">Abdulaziz S. Alobaid</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Jarrett, Paul" sort="Jarrett, Paul" uniqKey="Jarrett P" first="Paul" last="Jarrett">Paul Jarrett</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Stuart, Janine" sort="Stuart, Janine" uniqKey="Stuart J" first="Janine" last="Stuart">Janine Stuart</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Lassig Smith, Melissa" sort="Lassig Smith, Melissa" uniqKey="Lassig Smith M" first="Melissa" last="Lassig-Smith">Melissa Lassig-Smith</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Mejia, Jenny Lisette Ord Ez" sort="Mejia, Jenny Lisette Ord Ez" uniqKey="Mejia J" first="Jenny Lisette Ord Ez" last="Mejia">Jenny Lisette Ord Ez Mejia</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Roberts, Michael S" sort="Roberts, Michael S" uniqKey="Roberts M" first="Michael S." last="Roberts">Michael S. Roberts</name><affiliation><nlm:aff id="aff2">Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Sinnollareddy, Mahipal G" sort="Sinnollareddy, Mahipal G" uniqKey="Sinnollareddy M" first="Mahipal G." last="Sinnollareddy">Mahipal G. Sinnollareddy</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Roger, Claire" sort="Roger, Claire" uniqKey="Roger C" first="Claire" last="Roger">Claire Roger</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Department of Anesthesiology, Critical Care Pain, and Emergency Medicine, Nimes University Hospital, Nimes, France</nlm:aff></affiliation></author><author><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27550344</idno><idno type="pmc">5075058</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075058</idno><idno type="RBID">PMC:5075058</idno><idno type="doi">10.1128/AAC.01088-16</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">001746</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001746</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients</title><author><name sortKey="Alobaid, Abdulaziz S" sort="Alobaid, Abdulaziz S" uniqKey="Alobaid A" first="Abdulaziz S." last="Alobaid">Abdulaziz S. Alobaid</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C." last="Wallis">Steven C. Wallis</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Jarrett, Paul" sort="Jarrett, Paul" uniqKey="Jarrett P" first="Paul" last="Jarrett">Paul Jarrett</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Stuart, Janine" sort="Stuart, Janine" uniqKey="Stuart J" first="Janine" last="Stuart">Janine Stuart</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Lassig Smith, Melissa" sort="Lassig Smith, Melissa" uniqKey="Lassig Smith M" first="Melissa" last="Lassig-Smith">Melissa Lassig-Smith</name><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Mejia, Jenny Lisette Ord Ez" sort="Mejia, Jenny Lisette Ord Ez" uniqKey="Mejia J" first="Jenny Lisette Ord Ez" last="Mejia">Jenny Lisette Ord Ez Mejia</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Roberts, Michael S" sort="Roberts, Michael S" uniqKey="Roberts M" first="Michael S." last="Roberts">Michael S. Roberts</name><affiliation><nlm:aff id="aff2">Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Sinnollareddy, Mahipal G" sort="Sinnollareddy, Mahipal G" uniqKey="Sinnollareddy M" first="Mahipal G." last="Sinnollareddy">Mahipal G. Sinnollareddy</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia</nlm:aff></affiliation></author><author><name sortKey="Roger, Claire" sort="Roger, Claire" uniqKey="Roger C" first="Claire" last="Roger">Claire Roger</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Department of Anesthesiology, Critical Care Pain, and Emergency Medicine, Nimes University Hospital, Nimes, France</nlm:aff></affiliation></author><author><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A." last="Roberts">Jason A. Roberts</name><affiliation><nlm:aff id="aff1">Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia</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="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m<sup>2</sup>), obese (30.0 to 39.9 kg/m<sup>2</sup>), and morbidly obese (≥40 kg/m<sup>2</sup>). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (<italic>n</italic> = 6) and morbidly obese (<italic>n</italic> = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m<sup>2</sup>, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (<italic>V<sub>c</sub></italic>) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m<sup>2</sup>. A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.</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="iso-abbrev">Antimicrob. Agents Chemother</journal-id><journal-id journal-id-type="hwp">aac</journal-id><journal-id journal-id-type="pmc">aac</journal-id><journal-id journal-id-type="publisher-id">AAC</journal-id><journal-title-group><journal-title>Antimicrobial Agents and Chemotherapy</journal-title></journal-title-group><issn pub-type="ppub">0066-4804</issn><issn pub-type="epub">1098-6596</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27550344</article-id><article-id pub-id-type="pmc">5075058</article-id><article-id pub-id-type="publisher-id">01088-16</article-id><article-id pub-id-type="doi">10.1128/AAC.01088-16</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject></subj-group></article-categories><title-group><article-title>Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients</article-title><alt-title alt-title-type="running-head">Fluconazole PK in Obese ICU Patients</alt-title><alt-title alt-title-type="short-authors">Alobaid et al.</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Alobaid</surname><given-names>Abdulaziz S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wallis</surname><given-names>Steven C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jarrett</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Starr</surname><given-names>Therese</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Stuart</surname><given-names>Janine</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lassig-Smith</surname><given-names>Melissa</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mejia</surname><given-names>Jenny Lisette Ordóñez</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Roberts</surname><given-names>Michael S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sinnollareddy</surname><given-names>Mahipal G.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author"><name><surname>Roger</surname><given-names>Claire</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lipman</surname><given-names>Jeffrey</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Roberts</surname><given-names>Jason A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><aff id="aff1"><label>a</label>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia</aff><aff id="aff2"><label>b</label>Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia</aff><aff id="aff3"><label>c</label>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia</aff><aff id="aff4"><label>d</label>Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia</aff><aff id="aff5"><label>e</label>School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia</aff><aff id="aff6"><label>f</label>Department of Anesthesiology, Critical Care Pain, and Emergency Medicine, Nimes University Hospital, Nimes, France</aff><aff id="aff7"><label>g</label>School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia</aff></contrib-group><author-notes><corresp id="cor1">Address correspondence to Jason A. Roberts, <email>j.roberts2@uq.edu.au</email>.</corresp><fn fn-type="other"><p><bold>Citation</bold> Alobaid AS, Wallis SC, Jarrett P, Starr T, Stuart J, Lassig-Smith M, Mejia JLO, Roberts MS, Sinnollareddy MG, Roger C, Lipman J, Roberts JA. 2016. Effect of obesity on the population pharmacokinetics of fluconazole in critically ill patients. Antimicrob Agents Chemother 60:6550–6557. doi:<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1128/AAC.01088-16">10.1128/AAC.01088-16</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>22</day><month>8</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>21</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="collection"><month>11</month><year>2016</year></pub-date><volume>60</volume><issue>11</issue><fpage>6550</fpage><lpage>6557</lpage><history><date date-type="received"><day>20</day><month>5</month><year>2016</year></date><date date-type="rev-request"><day>16</day><month>6</month><year>2016</year></date><date date-type="accepted"><day>12</day><month>8</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2016, American Society for Microbiology. All Rights Reserved.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder></permissions><self-uri content-type="pdf" xlink:href="zac01116006550.pdf"></self-uri><abstract><p>Our objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m<sup>2</sup>), obese (30.0 to 39.9 kg/m<sup>2</sup>), and morbidly obese (≥40 kg/m<sup>2</sup>). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (<italic>n</italic> = 6) and morbidly obese (<italic>n</italic> = 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m<sup>2</sup>, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (<italic>V<sub>c</sub></italic>) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m<sup>2</sup>. A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.</p></abstract><funding-group><award-group id="award1"><funding-source id="gs1">Saudi Arabian Cultural Mission</funding-source><award-id rid="gs1">11984596</award-id><principal-award-recipient>Abdulaziz S. Alobaid</principal-award-recipient></award-group><award-group id="award2"><funding-source id="gs2">Department of Health | National Health and Medical Research Council (NHMRC)
<named-content content-type="funder-id">http://dx.doi.org/10.13039/501100000925</named-content></funding-source><award-id rid="gs2">APP1099452</award-id><award-id rid="gs2">APP1048652</award-id><award-id rid="gs2">APP1107356</award-id><principal-award-recipient>Jason A. Roberts</principal-award-recipient></award-group><award-group id="award3"><funding-source id="gs3">Intensive Care Foundation (ICF)
<named-content content-type="funder-id">http://dx.doi.org/10.13039/100009327</named-content></funding-source><principal-award-recipient>Jeffrey Lipman</principal-award-recipient></award-group></funding-group><counts><fig-count count="4"></fig-count><table-count count="5"></table-count><equation-count count="0"></equation-count><ref-count count="32"></ref-count><page-count count="8"></page-count><word-count count="6686"></word-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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