2012-06-01
Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B nor with ABCB1 in renal transplant recipients
Publication
Publication
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.
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doi.org/10.1097/FPC.0b013e32834a8650, hdl.handle.net/1765/68272 | |
Pharmacogenetics and Genomics | |
Organisation | Department of Clinical Chemistry |
Bouamar, R., Hesselink, D., van Schaik, R., Weimar, W., van der Heiden, I., de Fijter, J., … 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 |