Risk of diarrhoea in a long-term cohort of renal transplant patients given mycophenolate mofetil: The significant role of the UGT1A8*2 variant allele

British Journal of Clinical Pharmacology

Volumn 69, Issue 6, 2010, Pages 675-683

  Woillard, Jean Baptiste ^a,b   Rerolle, Jean Philippe ^a,c   Picard, Nicolas ^a,b,c   Rousseau, Annick ^a,b   Drouet, Mireille ^c,d   Munteanu, Eliza ^c   Essig, Marie ^a,c   Marquet, Pierre ^a,b,c   Le Meur, Yann ^a,e  

^a Univ Limoges   (France)

^b UNIVERSITY OF LIMOGES   (France)

^c LIMOGES UNIVERSITY HOSPITAL   (France)

^d CNRS   (France)

^e SERVICE DE RHUMATOLOGIE   (France)

Author keywords

Diarrhoea; Kidney transplantation; Mycophenolate mofetil; Pharmacogenetics; UGT1A8 2; Uridine diphosphate glucuronosyltransferase

Indexed keywords

ABC TRANSPORTER; CYCLOSPORIN A; GLUCURONOSYLTRANSFERASE 1A7; GLUCURONOSYLTRANSFERASE 1A8; GLUCURONOSYLTRANSFERASE 1A9; GLUCURONOSYLTRANSFERASE 2B7; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; TACROLIMUS;

ADULT; ALLELE; ARTICLE; BILIARY EXCRETION; CONTROLLED STUDY; DIARRHEA; DNA POLYMORPHISM; DRUG BILE LEVEL; DRUG EXCRETION; DRUG METABOLISM; FEMALE; GENE LINKAGE DISEQUILIBRIUM; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOTE; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY GRAFT; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; LINKAGE ANALYSIS; MAJOR CLINICAL STUDY; MALE; PHARMACOGENETICS; PRIORITY JOURNAL; PROPORTIONAL HAZARDS MODEL; RETROSPECTIVE STUDY; RISK ASSESSMENT; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; COHORT STUDIES; CYCLOSPORINE; DIARRHEA; DRUG COMBINATIONS; DRUG INTERACTIONS; FEMALE; GENOTYPE; GLUCURONOSYLTRANSFERASE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; MALE; MULTIVARIATE ANALYSIS; MYCOPHENOLIC ACID; POLYMORPHISM, SINGLE NUCLEOTIDE; PROPORTIONAL HAZARDS MODELS; RETROSPECTIVE STUDIES; RISK; SIROLIMUS; SURVIVAL ANALYSIS; TACROLIMUS;

EID: 77952051858     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2010.03625.x     Document Type: Article

References (26)

1. Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 1996 51 : 278 298. (Pubitemid 26039160)
2. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 1995 345 : 1321 1325.
3. Mathew TH. A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation: results at three years. Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Transplantation 1998 65 : 1450 1454.
4. van Gelder T, Hilbrands LB, Vanrenterghem Y, Weimar W, de Fijter JW, Squifflet JP, Hené RJ, Verpooten GA, Navarro MT, Hale MD, Nicholls AJ. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation 1999 68 : 261 266. (Pubitemid 29360288)
5. Borrows R, Chusney G, James A, Stichbury J, Van Tromp J, Cairns T, Griffith M, Hakim N, McLean A, Palmer A, Papalois V, Taube D. Determinants of mycophenolic acid levels after renal transplantation. Ther Drug Monit 2005 27 : 442 450. (Pubitemid 41098818)
6. Heller T, van Gelder T, Budde K, de Fijter JW, Kuypers D, Arns W, Schmidt J, Rostaing L, Powis SH, Claesson K, Macphee IA, Pohanka E, Engelmayer J, Brandhorst G, Oellerich M, Armstrong VW. Plasma concentrations of mycophenolic acid acyl glucuronide are not associated with diarrhea in renal transplant recipients. Am J Transplant 2007 7 : 1822 1831. (Pubitemid 46905448)
7. Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet 1998 34 : 429 455.
8. Picard N, Ratanasavanh D, Premaud A, Le Meur Y, Marquet P. Identification of the UDP-glucuronosyltransferase isoforms involved in mycophenolic acid phase II metabolism. Drug Metab Dispos 2005 33 : 139 146. (Pubitemid 40023525)
9. Bernard O, Guillemette C. The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos 2004 32 : 775 778. (Pubitemid 38955603)
10. Shipkova M, Armstrong VW, Wieland E, Niedmann PD, Schutz E, Brenner-Weiss G, Voihsel M, Braun F, Oellerich M. Identification of glucoside and carboxyl-linked glucuronide conjugates of mycophenolic acid in plasma of transplant recipients treated with mycophenolate mofetil. Br J Pharmacol 1999 126 : 1075 1082. (Pubitemid 29123740)
11. Ducloux D, Ottignon Y, Semhoun-Ducloux S, Labbe S, Saint-Hillier Y, Miguet JP, Carayon P, Chalopin JM. Mycophenolate mofetil-induced villous atrophy. Transplantation 1998 66 : 1115 1116. (Pubitemid 28513398)
12. Kamar N, Faure P, Dupuis E, Cointault O, Joseph-Hein K, Durand D, Moreau J, Rostaing L. Villous atrophy induced by mycophenolate mofetil in renal-transplant patients. Transpl Int 2004 17 : 463 467. (Pubitemid 39362576)
13. Maes BD, Dalle I, Geboes K, Oellerich M, Armstrong VW, Evenepoel P, Geypens B, Kuypers D, Shipkova M, Geboes K, Vanrenterghem YF. Erosive enterocolitis in mycophenolate mofetil-treated renal-transplant recipients with persistent afebrile diarrhea. Transplantation 2003 75 : 665 672. (Pubitemid 36337366)
14. Shipkova M, Armstrong VW, Weber L, Niedmann PD, Wieland E, Haley J, Tönshoff B, Oellerich M. Pharmacokinetics and protein adduct formation of the pharmacologically active acyl glucuronide metabolite of mycophenolic acid in pediatric renal transplant recipients. Ther Drug Monit 2002 24 : 390 399. (Pubitemid 34553205)
15. Wieland E, Shipkova M, Schellhaas U, Schutz E, Niedmann PD, Armstrong VW, Oellerich M. Induction of cytokine release by the acyl glucuronide of mycophenolic acid: a link to side effects? Clin Biochem 2000 33 : 107 113. (Pubitemid 30212818)
16. Shipkova M, Beck H, Voland A, Armstrong VW, Grone HJ, Oellerich M, Wieland E. Identification of protein targets for mycophenolic acid acyl glucuronide in rat liver and colon tissue. Proteomics 2004 4 : 2728 2738. (Pubitemid 39202173)
17. Hesselink DA, van Hest RM, Mathot RA, Bonthuis F, Weimar W, de Bruin RW, van Gelder T. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplant 2005 5 : 987 994. (Pubitemid 40571246)
18. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988 16 : 1215.
19. Tregouet DA, Escolano S, Tiret L, Mallet A, Golmard JL. A new algorithm for haplotype-based association analysis: the Stochastic-EM algorithm. Ann Hum Genet 2004 68 (Pt 2 165 177. (Pubitemid 38379847)
20. Helderman JH, Goral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002 13 : 277 287. (Pubitemid 34042039)
21. Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Neumayer, HH, Hauser I, Ericzon B, Brattström C, Claesson K, Mühlbacher F, Pohanka E. Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 1997 64 : 436 443. (Pubitemid 27349884)
22. Picard N, Premaud A, Rousseau A, Le Meur Y, Marquet P. A comparison of the effect of ciclosporin and sirolimus on the pharmokinetics of mycophenolate in renal transplant patients. Br J Clin Pharmacol 2006 62 : 477 484. (Pubitemid 44401531)
23. Hubner GI, Eismann R, Sziegoleit W. Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients. Ther Drug Monit 1999 21 : 536 539. (Pubitemid 29468321)
24. van Gelder T, Klupp J, Barten MJ, Christians U, Morris RE. Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid. Ther Drug Monit 2001 23 : 119 128. (Pubitemid 32240138)
25. Le Meur Y, Buchler M, Thierry A, Caillard S, Villemain F, Lavaud S, Etienne I, Westeel PF, Hurault de Ligny B, Rostaing L, Thervet E, Szelag JC, Rérolle JP, Rousseau A, Touchard G, Marquet P. Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation. Am J Transplant 2007 7 : 2496 2503. (Pubitemid 47566324)
26. Bernard O, Tojcic J, Journault K, Perusse L, Guillemette C. Influence of nonsynonymous polymorphisms of UGT1A8 and UGT2B7 metabolizing enzymes on the formation of phenolic and acyl glucuronides of mycophenolic acid. Drug Metab Dispos 2006 34 : 1539 1545. (Pubitemid 44285396)