FranceBresilV1, Main, Corpus, bibRecord, 002044

Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial

Identifieur interne : 002044 ( Main/Corpus ); précédent : 002043; suivant : 002045

Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial

Auteurs : RBID : Pascal:08-0510678

Descripteurs français

Pascal (Inist)
- Mycophénolate mofétil, Etude comparative, Immunodépresseur, Acide mycophénolique, Traitement, De novo, Mofétil, Transplantation, Homotransplantation, Rein, Dose, Protocole thérapeutique, Posologie, Concentration, Essai clinique, Greffe, Immunomodulateur, Antiviral, Antibiotique.

English descriptors

KwdEn :
- Antibiotic, Antiviral, Clinical trial, Comparative study, Concentration, De novo, Dose, Graft, Homotransplantation, Immunomodulator, Immunosuppressive agent, Kidney, Mofetil, Mycophenolate mofetil, Mycophenolic acid, Posology, Therapeutic protocol, Transplantation, Treatment.

Abstract

Background. Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. Methods. Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite ofbiopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. Results. Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). Conclusions. There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A11	`01`	`1`		`@1 VAN GELDER (Teun)`
A11	`02`	`1`		`@1 TEDESCO SILVA (Helio)`
A11	`03`	`1`		`@1 DE FIJTER (Johan W.)`
A11	`04`	`1`		`@1 BUDDE (Klemens)`
A11	`05`	`1`		`@1 KUYPERS (Dirk)`
A11	`06`	`1`		`@1 TYDEN (Gunnar)`
A11	`07`	`1`		`@1 LOHMUS (Aleksander)`
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A11	`10`	`1`		`@1 LE MEUR (Yann)`
A11	`11`	`1`		`@1 OELLERICH (Michael)`
A11	`12`	`1`		`@1 HOLT (David W.)`
A11	`13`	`1`		`@1 TÖNSHOFF (Burkhard)`
A11	`14`	`1`		`@1 KEOWN (Paul)`
A11	`15`	`1`		`@1 CAMPBELL (Scott)`
A11	`16`	`1`		`@1 MAMELOK (Richard D.)`
A14	`01`			`@1 Departments of Hospital Pharmacy and Internal Medicine, Erasmus Medical Center @2 Rotterdam @3 NLD @Z 1 aut.`
A14	`02`			`@1 Department of Nephrology, Hospital do Rim e Hipertensao @2 São Paulo @3 BRA @Z 2 aut.`
A14	`03`			`@1 Department of Nephrology, Leiden University Medical Center @3 NLD @Z 3 aut.`
A14	`04`			`@1 Department of Nephrology, Charité University @2 Berlin @3 DEU @Z 4 aut.`
A14	`05`			`@1 Department of Nephrology and Renal Transplantation, Leuven University @3 BEL @Z 5 aut.`
A14	`06`			`@1 Department of Transplantation, Karolinksa University @2 Stockholm @3 SWE @Z 6 aut.`
A14	`07`			`@1 Department of Nephrology @2 Tartu @3 EST @Z 7 aut.`
A14	`08`			`@1 Department of Nephrology, University of Heidelberg @2 Heidelberg @3 DEU @Z 8 aut.`
A14	`09`			`@1 Department of Medicine, Rikshospitalet, University of Oslo @3 NOR @Z 9 aut.`
A14	`10`			`@1 Department of Nephrology, Central University Hospital Dupuytren @2 Limoges @3 FRA @Z 10 aut.`
A14	`11`			`@1 Department of Clinical Chemistry, Georg-August-Universität Göttingen @3 DEU @Z 11 aut.`
A14	`12`			`@1 Analytical Unit, St George's University of London @2 London @3 GBR @Z 12 aut.`
A14	`13`			`@1 University Children's Hospital @2 Heidelberg @3 DEU @Z 13 aut.`
A14	`14`			`@1 University Hospital Vancouver @3 CAN @Z 14 aut.`
A14	`15`			`@1 Department of Nephrology, University of Queensland @2 Brisbane @3 AUS @Z 15 aut.`
A14	`16`			`@1 Mamelok Consulting @2 Palo Alto, CA @3 USA @Z 16 aut.`
A20				`@1 1043-1051`
A21				`@1 2008`
A23	`01`			`@0 ENG`
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A44				`@0 0000 @1 © 2008 INIST-CNRS. All rights reserved.`
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C01	`01`		`ENG`	@0 Background. Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. Methods. Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite ofbiopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. Results. Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). Conclusions. There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.
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Format Inist (serveur)

NO :	PASCAL 08-0510678 INIST
ET :	Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial
AU :	VAN GELDER (Teun); TEDESCO SILVA (Helio); DE FIJTER (Johan W.); BUDDE (Klemens); KUYPERS (Dirk); TYDEN (Gunnar); LOHMUS (Aleksander); SOMMERER (Claudia); HARTMANN (Anders); LE MEUR (Yann); OELLERICH (Michael); HOLT (David W.); TÖNSHOFF (Burkhard); KEOWN (Paul); CAMPBELL (Scott); MAMELOK (Richard D.)
AF :	Departments of Hospital Pharmacy and Internal Medicine, Erasmus Medical Center/Rotterdam/Pays-Bas (1 aut.); Department of Nephrology, Hospital do Rim e Hipertensao/São Paulo/Brésil (2 aut.); Department of Nephrology, Leiden University Medical Center/Pays-Bas (3 aut.); Department of Nephrology, Charité University/Berlin/Allemagne (4 aut.); Department of Nephrology and Renal Transplantation, Leuven University/Belgique (5 aut.); Department of Transplantation, Karolinksa University/Stockholm/Suède (6 aut.); Department of Nephrology/Tartu/Estonie (7 aut.); Department of Nephrology, University of Heidelberg/Heidelberg/Allemagne (8 aut.); Department of Medicine, Rikshospitalet, University of Oslo/Norvège (9 aut.); Department of Nephrology, Central University Hospital Dupuytren/Limoges/France (10 aut.); Department of Clinical Chemistry, Georg-August-Universität Göttingen/Allemagne (11 aut.); Analytical Unit, St George's University of London/London/Royaume-Uni (12 aut.); University Children's Hospital/Heidelberg/Allemagne (13 aut.); University Hospital Vancouver/Canada (14 aut.); Department of Nephrology, University of Queensland/Brisbane/Australie (15 aut.); Mamelok Consulting/Palo Alto, CA/Etats-Unis (16 aut.)
DT :	Publication en série; Niveau analytique
SO :	Transplantation; ISSN 0041-1337; Coden TRPLAU; Etats-Unis; Da. 2008; Vol. 86; No. 8; Pp. 1043-1051; Bibl. 21 ref.
LA :	Anglais
EA :	Background. Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. Methods. Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite ofbiopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. Results. Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). Conclusions. There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.
CC :	002B25; 002A06F; 002B02S05
FD :	Mycophénolate mofétil; Etude comparative; Immunodépresseur; Acide mycophénolique; Traitement; De novo; Mofétil; Transplantation; Homotransplantation; Rein; Dose; Protocole thérapeutique; Posologie; Concentration; Essai clinique; Greffe; Immunomodulateur; Antiviral; Antibiotique
FG :	Inhibiteur enzyme; IMP dehydrogenase; Oxidoreductases; Enzyme; Chirurgie; Appareil urinaire
ED :	Mycophenolate mofetil; Comparative study; Immunosuppressive agent; Mycophenolic acid; Treatment; De novo; Mofetil; Transplantation; Homotransplantation; Kidney; Dose; Therapeutic protocol; Posology; Concentration; Clinical trial; Graft; Immunomodulator; Antiviral; Antibiotic
EG :	Enzyme inhibitor; IMP dehydrogenase; Oxidoreductases; Enzyme; Surgery; Urinary system
SD :	Micofenolato mofetil; Estudio comparativo; Inmunodepresor; Acido micofenólico; Tratamiento; De novo; Mofetilo; Trasplantación; Homotrasplante; Riñón; Dosis; Protocolo terapéutico; Posología; Concentración; Ensayo clínico; Injerto; Inmunomodulador; Antiviral; Antibiótico
LO :	INIST-8318.354000184460140050
ID :	08-0510678

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Pascal:08-0510678

Le document en format XML

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<author><name sortKey="Tedesco Silva, Helio" uniqKey="Tedesco Silva H">Helio Tedesco Silva</name>
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<author><name sortKey="De Fijter, Johan W" uniqKey="De Fijter J">Johan W. De Fijter</name>
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<author><name sortKey="Budde, Klemens" uniqKey="Budde K">Klemens Budde</name>
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<author><name sortKey="Kuypers, Dirk" uniqKey="Kuypers D">Dirk Kuypers</name>
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<author><name sortKey="Tyden, Gunnar" uniqKey="Tyden G">Gunnar Tyden</name>
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<author><name sortKey="Lohmus, Aleksander" uniqKey="Lohmus A">Aleksander Lohmus</name>
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<author><name sortKey="Sommerer, Claudia" uniqKey="Sommerer C">Claudia Sommerer</name>
<affiliation><inist:fA14 i1="08"><s1>Department of Nephrology, University of Heidelberg</s1>
<s2>Heidelberg</s2>
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<author><name sortKey="Hartmann, Anders" uniqKey="Hartmann A">Anders Hartmann</name>
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<author><name sortKey="Le Meur, Yann" uniqKey="Le Meur Y">Yann Le Meur</name>
<affiliation><inist:fA14 i1="10"><s1>Department of Nephrology, Central University Hospital Dupuytren</s1>
<s2>Limoges</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Oellerich, Michael" uniqKey="Oellerich M">Michael Oellerich</name>
<affiliation><inist:fA14 i1="11"><s1>Department of Clinical Chemistry, Georg-August-Universität Göttingen</s1>
<s3>DEU</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Holt, David W" uniqKey="Holt D">David W. Holt</name>
<affiliation><inist:fA14 i1="12"><s1>Analytical Unit, St George's University of London</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
<author><name sortKey="Tonshoff, Burkhard" uniqKey="Tonshoff B">Burkhard Tönshoff</name>
<affiliation><inist:fA14 i1="13"><s1>University Children's Hospital</s1>
<s2>Heidelberg</s2>
<s3>DEU</s3>
<sZ>13 aut.</sZ>
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</affiliation>
</author>
<author><name sortKey="Keown, Paul" uniqKey="Keown P">Paul Keown</name>
<affiliation><inist:fA14 i1="14"><s1>University Hospital Vancouver</s1>
<s3>CAN</s3>
<sZ>14 aut.</sZ>
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</affiliation>
</author>
<author><name sortKey="Campbell, Scott" uniqKey="Campbell S">Scott Campbell</name>
<affiliation><inist:fA14 i1="15"><s1>Department of Nephrology, University of Queensland</s1>
<s2>Brisbane</s2>
<s3>AUS</s3>
<sZ>15 aut.</sZ>
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</affiliation>
</author>
<author><name sortKey="Mamelok, Richard D" uniqKey="Mamelok R">Richard D. Mamelok</name>
<affiliation><inist:fA14 i1="16"><s1>Mamelok Consulting</s1>
<s2>Palo Alto, CA</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="inist">08-0510678</idno>
<date when="2008">2008</date>
<idno type="stanalyst">PASCAL 08-0510678 INIST</idno>
<idno type="RBID">Pascal:08-0510678</idno>
<idno type="wicri:Area/Main/Corpus">002044</idno>
</publicationStmt>
<seriesStmt><idno type="ISSN">0041-1337</idno>
<title level="j" type="abbreviated">Transplantation</title>
<title level="j" type="main">Transplantation</title>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibiotic</term>
<term>Antiviral</term>
<term>Clinical trial</term>
<term>Comparative study</term>
<term>Concentration</term>
<term>De novo</term>
<term>Dose</term>
<term>Graft</term>
<term>Homotransplantation</term>
<term>Immunomodulator</term>
<term>Immunosuppressive agent</term>
<term>Kidney</term>
<term>Mofetil</term>
<term>Mycophenolate mofetil</term>
<term>Mycophenolic acid</term>
<term>Posology</term>
<term>Therapeutic protocol</term>
<term>Transplantation</term>
<term>Treatment</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Mycophénolate mofétil</term>
<term>Etude comparative</term>
<term>Immunodépresseur</term>
<term>Acide mycophénolique</term>
<term>Traitement</term>
<term>De novo</term>
<term>Mofétil</term>
<term>Transplantation</term>
<term>Homotransplantation</term>
<term>Rein</term>
<term>Dose</term>
<term>Protocole thérapeutique</term>
<term>Posologie</term>
<term>Concentration</term>
<term>Essai clinique</term>
<term>Greffe</term>
<term>Immunomodulateur</term>
<term>Antiviral</term>
<term>Antibiotique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background. Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. Methods. Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite ofbiopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. Results. Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). Conclusions. There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0041-1337</s0>
</fA01>
<fA02 i1="01"><s0>TRPLAU</s0>
</fA02>
<fA03 i2="1"><s0>Transplantation</s0>
</fA03>
<fA05><s2>86</s2>
</fA05>
<fA06><s2>8</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>VAN GELDER (Teun)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>TEDESCO SILVA (Helio)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>DE FIJTER (Johan W.)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>BUDDE (Klemens)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>KUYPERS (Dirk)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>TYDEN (Gunnar)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>LOHMUS (Aleksander)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>SOMMERER (Claudia)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>HARTMANN (Anders)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>LE MEUR (Yann)</s1>
</fA11>
<fA11 i1="11" i2="1"><s1>OELLERICH (Michael)</s1>
</fA11>
<fA11 i1="12" i2="1"><s1>HOLT (David W.)</s1>
</fA11>
<fA11 i1="13" i2="1"><s1>TÖNSHOFF (Burkhard)</s1>
</fA11>
<fA11 i1="14" i2="1"><s1>KEOWN (Paul)</s1>
</fA11>
<fA11 i1="15" i2="1"><s1>CAMPBELL (Scott)</s1>
</fA11>
<fA11 i1="16" i2="1"><s1>MAMELOK (Richard D.)</s1>
</fA11>
<fA14 i1="01"><s1>Departments of Hospital Pharmacy and Internal Medicine, Erasmus Medical Center</s1>
<s2>Rotterdam</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Department of Nephrology, Hospital do Rim e Hipertensao</s1>
<s2>São Paulo</s2>
<s3>BRA</s3>
<sZ>2 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Department of Nephrology, Leiden University Medical Center</s1>
<s3>NLD</s3>
<sZ>3 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Department of Nephrology, Charité University</s1>
<s2>Berlin</s2>
<s3>DEU</s3>
<sZ>4 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Department of Nephrology and Renal Transplantation, Leuven University</s1>
<s3>BEL</s3>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="06"><s1>Department of Transplantation, Karolinksa University</s1>
<s2>Stockholm</s2>
<s3>SWE</s3>
<sZ>6 aut.</sZ>
</fA14>
<fA14 i1="07"><s1>Department of Nephrology</s1>
<s2>Tartu</s2>
<s3>EST</s3>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="08"><s1>Department of Nephrology, University of Heidelberg</s1>
<s2>Heidelberg</s2>
<s3>DEU</s3>
<sZ>8 aut.</sZ>
</fA14>
<fA14 i1="09"><s1>Department of Medicine, Rikshospitalet, University of Oslo</s1>
<s3>NOR</s3>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="10"><s1>Department of Nephrology, Central University Hospital Dupuytren</s1>
<s2>Limoges</s2>
<s3>FRA</s3>
<sZ>10 aut.</sZ>
</fA14>
<fA14 i1="11"><s1>Department of Clinical Chemistry, Georg-August-Universität Göttingen</s1>
<s3>DEU</s3>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="12"><s1>Analytical Unit, St George's University of London</s1>
<s2>London</s2>
<s3>GBR</s3>
<sZ>12 aut.</sZ>
</fA14>
<fA14 i1="13"><s1>University Children's Hospital</s1>
<s2>Heidelberg</s2>
<s3>DEU</s3>
<sZ>13 aut.</sZ>
</fA14>
<fA14 i1="14"><s1>University Hospital Vancouver</s1>
<s3>CAN</s3>
<sZ>14 aut.</sZ>
</fA14>
<fA14 i1="15"><s1>Department of Nephrology, University of Queensland</s1>
<s2>Brisbane</s2>
<s3>AUS</s3>
<sZ>15 aut.</sZ>
</fA14>
<fA14 i1="16"><s1>Mamelok Consulting</s1>
<s2>Palo Alto, CA</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
</fA14>
<fA20><s1>1043-1051</s1>
</fA20>
<fA21><s1>2008</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>8318</s2>
<s5>354000184460140050</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2008 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>21 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>08-0510678</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Transplantation</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>Background. Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. Methods. Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite ofbiopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. Results. Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). Conclusions. There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B25</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002A06F</s0>
</fC02>
<fC02 i1="03" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Mycophénolate mofétil</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Mycophenolate mofetil</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Micofenolato mofetil</s0>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Etude comparative</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Comparative study</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Estudio comparativo</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Immunodépresseur</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Immunosuppressive agent</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Inmunodepresor</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Acide mycophénolique</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Mycophenolic acid</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Acido micofenólico</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Traitement</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Treatment</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Tratamiento</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>De novo</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>De novo</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>De novo</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Mofétil</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Mofetil</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Mofetilo</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Transplantation</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Transplantation</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Trasplantación</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Homotransplantation</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Homotransplantation</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Homotrasplante</s0>
<s5>09</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Rein</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Kidney</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Riñón</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Dose</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Dose</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Dosis</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Protocole thérapeutique</s0>
<s5>13</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Therapeutic protocol</s0>
<s5>13</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Protocolo terapéutico</s0>
<s5>13</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Posologie</s0>
<s5>17</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG"><s0>Posology</s0>
<s5>17</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA"><s0>Posología</s0>
<s5>17</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Concentration</s0>
<s5>18</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Concentration</s0>
<s5>18</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Concentración</s0>
<s5>18</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE"><s0>Essai clinique</s0>
<s5>19</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG"><s0>Clinical trial</s0>
<s5>19</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA"><s0>Ensayo clínico</s0>
<s5>19</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE"><s0>Greffe</s0>
<s5>25</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG"><s0>Graft</s0>
<s5>25</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA"><s0>Injerto</s0>
<s5>25</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE"><s0>Immunomodulateur</s0>
<s5>26</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG"><s0>Immunomodulator</s0>
<s5>26</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA"><s0>Inmunomodulador</s0>
<s5>26</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE"><s0>Antiviral</s0>
<s5>27</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG"><s0>Antiviral</s0>
<s5>27</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>27</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE"><s0>Antibiotique</s0>
<s5>28</s5>
</fC03>
<fC03 i1="19" i2="X" l="ENG"><s0>Antibiotic</s0>
<s5>28</s5>
</fC03>
<fC03 i1="19" i2="X" l="SPA"><s0>Antibiótico</s0>
<s5>28</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Enzyme inhibitor</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Inhibidor enzima</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>IMP dehydrogenase</s0>
<s2>FE</s2>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>IMP dehydrogenase</s0>
<s2>FE</s2>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>IMP dehydrogenase</s0>
<s2>FE</s2>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Chirurgie</s0>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Surgery</s0>
<s5>39</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Cirugía</s0>
<s5>39</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Appareil urinaire</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Urinary system</s0>
<s5>40</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Aparato urinario</s0>
<s5>40</s5>
</fC07>
<fN21><s1>336</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
<server><NO>PASCAL 08-0510678 INIST</NO>
<ET>Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial</ET>
<AU>VAN GELDER (Teun); TEDESCO SILVA (Helio); DE FIJTER (Johan W.); BUDDE (Klemens); KUYPERS (Dirk); TYDEN (Gunnar); LOHMUS (Aleksander); SOMMERER (Claudia); HARTMANN (Anders); LE MEUR (Yann); OELLERICH (Michael); HOLT (David W.); TÖNSHOFF (Burkhard); KEOWN (Paul); CAMPBELL (Scott); MAMELOK (Richard D.)</AU>
<AF>Departments of Hospital Pharmacy and Internal Medicine, Erasmus Medical Center/Rotterdam/Pays-Bas (1 aut.); Department of Nephrology, Hospital do Rim e Hipertensao/São Paulo/Brésil (2 aut.); Department of Nephrology, Leiden University Medical Center/Pays-Bas (3 aut.); Department of Nephrology, Charité University/Berlin/Allemagne (4 aut.); Department of Nephrology and Renal Transplantation, Leuven University/Belgique (5 aut.); Department of Transplantation, Karolinksa University/Stockholm/Suède (6 aut.); Department of Nephrology/Tartu/Estonie (7 aut.); Department of Nephrology, University of Heidelberg/Heidelberg/Allemagne (8 aut.); Department of Medicine, Rikshospitalet, University of Oslo/Norvège (9 aut.); Department of Nephrology, Central University Hospital Dupuytren/Limoges/France (10 aut.); Department of Clinical Chemistry, Georg-August-Universität Göttingen/Allemagne (11 aut.); Analytical Unit, St George's University of London/London/Royaume-Uni (12 aut.); University Children's Hospital/Heidelberg/Allemagne (13 aut.); University Hospital Vancouver/Canada (14 aut.); Department of Nephrology, University of Queensland/Brisbane/Australie (15 aut.); Mamelok Consulting/Palo Alto, CA/Etats-Unis (16 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Transplantation; ISSN 0041-1337; Coden TRPLAU; Etats-Unis; Da. 2008; Vol. 86; No. 8; Pp. 1043-1051; Bibl. 21 ref.</SO>
<LA>Anglais</LA>
<EA>Background. Fixed-dose mycophenolate mofetil (MMF) reduces the incidence of acute rejection after solid organ transplantation. The Fixed-Dose Concentration Controlled trial assessed the feasibility and potential benefit of therapeutic drug monitoring in patients receiving MMF after de novo renal transplant. Methods. Patients were randomized to a concentration-controlled (n=452; target exposure 45 mg hr/L) or a fixed-dose (n=449) MMF-containing regimen. The primary endpoint was treatment failure (a composite ofbiopsy-proven acute rejection [BPAR], graft loss, death, or MMF discontinuation) by 12 months posttransplantation. Results. Mycophenolic acid (MPA) exposures for both groups were similar at most time points and were below 30 mg hr/L in 37.3% of patients at day 3. There was no difference in the incidence of treatment failure (25.6% vs. 25.7%, P=0.81) or BPAR (14.9% vs. 15.5%, P>0.05) between the concentration-controlled and the fixed-dose groups, respectively. We did find a significant relationship between MPA-area under the concentration-time curve on day 3 and the incidence of BPAR in the first month (P=0.009) or in the first year posttransplantation (P=0.006). For later time points (day 10, month 1) there was no significant relationship between area under the concentration-time curve and BPAR (0.2572 and 0.5588, respectively). Conclusions. There was no difference in the incidence of treatment failure between the concentration-controlled and the fixed-dose groups. The applied protocol of MMF dose adjustments based on target MPA exposure was not successful, partly because physicians seemed reluctant to implement substantial dose changes. Current initial MMF doses underexpose more than 35% of patients early after transplantation, increasing the risk for BPAR.</EA>
<CC>002B25; 002A06F; 002B02S05</CC>
<FD>Mycophénolate mofétil; Etude comparative; Immunodépresseur; Acide mycophénolique; Traitement; De novo; Mofétil; Transplantation; Homotransplantation; Rein; Dose; Protocole thérapeutique; Posologie; Concentration; Essai clinique; Greffe; Immunomodulateur; Antiviral; Antibiotique</FD>
<FG>Inhibiteur enzyme; IMP dehydrogenase; Oxidoreductases; Enzyme; Chirurgie; Appareil urinaire</FG>
<ED>Mycophenolate mofetil; Comparative study; Immunosuppressive agent; Mycophenolic acid; Treatment; De novo; Mofetil; Transplantation; Homotransplantation; Kidney; Dose; Therapeutic protocol; Posology; Concentration; Clinical trial; Graft; Immunomodulator; Antiviral; Antibiotic</ED>
<EG>Enzyme inhibitor; IMP dehydrogenase; Oxidoreductases; Enzyme; Surgery; Urinary system</EG>
<SD>Micofenolato mofetil; Estudio comparativo; Inmunodepresor; Acido micofenólico; Tratamiento; De novo; Mofetilo; Trasplantación; Homotrasplante; Riñón; Dosis; Protocolo terapéutico; Posología; Concentración; Ensayo clínico; Injerto; Inmunomodulador; Antiviral; Antibiótico</SD>
<LO>INIST-8318.354000184460140050</LO>
<ID>08-0510678</ID>
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Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial

Comparing Mycophenolate Mofetil Regimens for de Novo Renal Transplant Recipients : The Fixed-Dose Concentration-Controlled Trial

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