Genetic polymorphisms influence mycophenolate mofetil-related adverse events in pediatric heart transplant patients

Journal of Heart and Lung Transplantation

Volumn 29, Issue 5, 2010, Pages 509-516

  Ohmann, Erin L ^a   Burckart, Gilbert J ^b   Brooks, Maria M ^c   Chen, Yan ^d   Pravica, Vera ^d   Girnita, Diana M ^a   Zeevi, Adriana ^a   Webber, Steven A ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^c UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^d UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

ABCC2; adverse events; genetic polymorphism; inosine monophosphate dehydrogenase 1; inosine monophosphate dehydrogenase 2; multidrug resistance protein 2; mycophenolate mofetil

Indexed keywords

CYCLOSPORIN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; TACROLIMUS;

ABCC2 GENE; ABDOMINAL PAIN; ANEMIA; ARTICLE; BONE MARROW SUPPRESSION; CARDIAC GRAFT REJECTION; CHILD; CONTROLLED STUDY; DIARRHEA; DRUG SUBSTITUTION; DRUG WITHDRAWAL; FEMALE; GENE; GENE FREQUENCY; GENOTYPE; GRAFT RECIPIENT; HEART TRANSPLANTATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IMPDH1 GENE; IMPDH2 GENE; INFANT; LEUKOPENIA; MAJOR CLINICAL STUDY; MALE; NAUSEA; NEUTROPENIA; PRESCHOOL CHILD; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; SCHOOL CHILD; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOCYTOPENIA; VOMITING;

ADOLESCENT; ALLELES; BONE MARROW CELLS; CHILD; CHILD, PRESCHOOL; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; GASTROENTERITIS; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HEART TRANSPLANTATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMP DEHYDROGENASE; INFANT; MALE; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; MYCOPHENOLIC ACID; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 77950520590     PISSN: 10532498     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.healun.2009.11.602     Document Type: Article

References (44)

1. Boucek M.M., Aurora P., Edwards L.B., et al. Registry of the International Society for Heart and Lung Transplantation: tenth official pediatric heart transplantation report-2007. J Heart Lung Transplant 26 (2007) 796-807
2. Allison A.C., and Eugui E.M. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47 (2000) 85-118
3. Browne B.J. The Tricontinental Mycophenolate Mofetil Trial. Transplantation 62 (1996) 1697
4. Dipchand A.I., Benson L., McCrindle B.W., et al. Mycophenolate mofetil in pediatric heart transplant recipients: a single-center experience. Pediatr Transplant 5 (2001) 112-118
5. Kobashigawa J.A., and Meiser B.M. Review of major clinical trials with mycophenolate mofetil in cardiac transplantation. Transplantation 80 suppl (2005) S235-S243
6. Meur Y.L., Büchler M., Thierry A., et al. Individualized mycophenolate mofetil dosing based on drug exposure significantly improves patient outcomes after renal transplantation. Am J Transplant 7 (2007) 2496-2503
7. van Gelder T., Silva H.T., de Fijter J.W., et al. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial. Transplantation 86 (2008) 1043-1051
8. Hesselink D.A., and van Gelder T. Genetic and nongenetic determinants of between-patient variability in the pharmacokinetics of mycophenolic acid. Clin Pharmacol Ther 78 (2005) 317-321
9. Kuypers D.R.J., Naesens M., Vermeire S., et al. The impact of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T on early mycophenolic acid dose-interval exposure in de novo renal allograft recipients. Clin Pharmacol Ther 78 (2005) 351-361
10. Levesque E., Delage R., Benoit-Biancamano M.O., et al. The impact of UGT1A8, UGT1A9, and UGT2B7 genetic polymorphisms on the pharmacokinetic profile of mycophenolic acid after a single oral dose in healthy volunteers. Clin Pharmacol Ther 81 (2007) 392-400
11. Kagaya H., Inoue K., Miura M., et al. Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol 63 (2007) 279-288
12. Bernard O., Tojcic J., Journault K., et al. Influence of nonsynonymous polymorphisms of UGT1A8 and UGT2B7 metabolizing enzymes on the formation of phenolic and acyl glucuronides of mycophenolic acid. Drug Metabol Dispos 34 (2006) 1539-1545
13. Djebli N., Picard N., Rerolle J.-P., et al. Influence of the UGT2B7 promoter region and exon 2 polymorphisms and comedications on acyl-MPAG production in vitro and in adult renal transplant patients. Pharmacogenet Genom 17 (2007) 321-330
14. Naesens M., Kuypers D.R.J., Verbeke K., et al. Multidrug resistance protein 2 genetic polymorphisms influence mycophenolic acid exposure in renal allograft recipients. Transplantation 82 (2006) 1074-1084
15. Sai K., Saito Y., Itoda M., et al. Genetic variations and haplotypes of ABCC2 encoding MRP2 in a Japanese population. Drug Metab Pharmacokin 23 (2008) 139-147
16. Miura M., Satoh S., Inoue K., et al. Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol 63 (2007) 1161-1169
17. Wang J., Yang J.W., Zeevi A., et al. IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients. Clin Pharmacol Ther 83 (2008) 711-717
18. Wang J.A., Zeevi A.C., Webber S.C., et al. A novel variant L263F in human inosine 5'-monophosphate dehydrogenase 2 is associated with diminished enzyme activity. Pharmacogenet Genom 17 (2007) 283-290
19. Common terminology criteria for adverse events version 3.0 (CTCAE), August 9, 2006 (2006), National Cancer Institute
20. Hesselink D.A., van Hest R.M., Mathot R.A.A., et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplant 5 (2005) 987-994
21. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 61 (1996) 1029-1037
22. Eisen H.J., Kobashigawa J., Keogh A., et al. Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. J Heart Lung Transplant 24 (2005) 517-525
23. Kobashigawa J., Miller L., Renlund D., et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Transplantation 66 (1998) 507-515
24. Keogh A. Long-term benefits of mycophenolate mofetil after heart transplantation. [erratum appears in Transplantation. 2005 Apr 27;79(8):986]. Transplantation 79 suppl (2005) S45-S46
25. Weimer R., Mytilineos J., Feustel A., et al. Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients. Transplantation 75 (2003) 2090-2099
26. Roth D., Colona J., Burke G.W., et al. Primary immunosuppression with tacrolimus and mycophenolate mofetil for renal allograft recipients. Transplantation 65 (1998) 248-252
27. Butani L., Palmer J., Baluarte H.J., et al. Adverse effects of mycophenolate mofetil in pediatric renal transplant recipients with presumed chronic rejection. Transplantation 68 (1999) 83-86
28. Kim J.J., Dreyer W.J., O'Brian Smith E., et al. Leukocyte suppression is associated with improved clinical outcomes in children's status after orthotopic heart transplantation. J Heart Lung Transplant 25 (2006) 195-199
29. van Gelder T., Hilbrands L.B., Vanrenterghem Y., et al. 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 68 (1999) 261-266
30. Sombogaard F., van Schaik R.H., Mathot R.A., et al. Interpatient variability in IMPDH activity in MMF-treated renal transplant patients is correlated with IMPDH type II 3757T > C polymorphism. Pharmacogenet Genom 19 (2009) 626-634
31. Weber L.T., Shipkova M., Armstrong V.W., et al. The pharmacokinetic-pharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients: a report of the German Study Group on Mycophenolate Mofetil Therapy. J Am Soc Nephrol 13 (2002) 759-768
32. Cattaneo D., Gaspari F., Ferrari S., et al. Pharmacokinetics help optimizing mycophenolate mofetil dosing in kidney transplant patients. Clin Transplant 15 (2001) 402-409
33. Bunnapradist S., Lentine K.L., Burroughs T.E., et al. Mycophenolate mofetil dose reductions and discontinuations after gastrointestinal complications are associated with renal transplant graft failure. Transplantation 82 (2006) 102-107
34. Galiwango P.J., Delgado D.H., Yan R., et al. Mycophenolate mofetil dose reduction for gastrointestinal intolerance is associated with increased rates of rejection in heart transplant patients. J Heart Lung Transplant 27 (2008) 72-77
35. Knoll G.A., MacDonald I., Khan A., et al. Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation. J Am Soc Nephrol 14 (2003) 2381-2386
36. Gajarski R.J., Crowley D.C., Zamberlan M.C., et al. Lack of correlation between MMF dose and MPA level in pediatric and young adult cardiac transplant patients: does the MPA level matter?. Am J Transplant 4 (2004) 1495-1500
37. Neerman M.F., and Boothe D.M. A possible mechanism of gastrointestinal toxicity posed by mycophenolic acid [erratum appears in Pharmacol Res. 2003 Oct;48(4):415]. Pharmacol Res 47 (2003) 523-526
38. Westley I.S., Brogan L.R., Morris R.G., et al. Role of Mrp2 in the hepatic disposition of mycophenolic acid and its glucuronide metabolites: effect of cyclosporine. Drug Metabol Dispos 34 (2006) 261-266
39. Shipkova M., Spielbauer B., Voland A., et al. cDNA microarray analysis reveals new candidate genes possibly linked to side effects under mycophenolate mofetil therapy. Transplantation 78 (2004) 1145-1152
40. Shipkova M., Armstrong V.W., Oellerich M., et al. Acyl glucuronide drug metabolites: toxicological and analytical implications. Ther Drug Monit 25 (2003) 1-16
41. Wieland E., Shipkova M., Schellhaas U., et al. Induction of cytokine release by the acyl glucuronide of mycophenolic acid: a link to side effects?. Clin Biochem 33 (2000) 107-113
42. Grinyo J.M., Ekberg H., Mamelok R.D., et al. The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony Pharmacokinetic Substudy. Nephrol Dial Transplant 24 (2009) 2269-2276
43. Girnita D.M., Brooks M.M., Webber S.A., et al. Genetic polymorphisms impact the risk of acute rejection in pediatric heart transplantation: a multi-institutional study. Transplantation 85 (2008) 1632-1639
44. Girnita D.M., Webber S.A., Ferrell R., et al. Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients. Transplantation 82 (2006) 1774-1780