Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients
Pharmacogenetics and Genomics , Volume 22 - Issue 6 p. 399- 407
OBJECTIVE: We investigated the association between genetic polymorphisms in ABCB1 and SLCO1B and mycophenolic acid (MPA) pharmacokinetics, and MPA-related diarrhea and leukopenia in 338 kidney transplant recipients. METHODS: A total of 338 patients participating in an international, randomized-controlled clinical trial were genotyped for ABCB1 and SLCO1B. Patients were all treated with mycophenolate mofetil and either cyclosporine or tacrolimus. MPA-area under the curve (AUCs), MPA-glucuronide AUCs and acylglucuronide-AUCs were measured on days 3 and 10, and months 1, 3, 6, and 12 after kidney transplantation. RESULTS: The risk of developing diarrhea was 1.8-fold higher in patients cotreated with tacrolimus compared with patients cotreated with cyclosporine (95% confidence interval: 1.03-3.13; P=0.038). ABCB1 and SLCO1B SNPs were not associated with dose-adjusted exposure to MPA, MPA-glucuronide, nor acylglucuronide-MPA nor with the incidence of diarrhea or leukopenia. CONCLUSION: Genotyping for ABCB1 or SLCO1B pretransplantation is unlikely to be of clinical value for individualization of MPA therapy.
|ABCB1, Diarrhea, Leukopenia, Mycophenolate mofetil, Mycophenolic acid, Pharmacogenetics, Pharmacokinetics, SLCO1B, Transplantation|
|Pharmacogenetics and Genomics|
|Organisation||Department of Clinical Chemistry|
Bouamar, R, Hesselink, D.A, van Schaik, R.H.N, Weimar, W, van der Heiden, I.P, de Fijter, J.W, … van Gelder, T. (2012). Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients. Pharmacogenetics and Genomics, 22(6), 399–407. doi:10.1097/FPC.0b013e32834a8650