Polymorphisms in CYP3A5, CYP3A4, and ABCB1 Are Not Associated with Cyclosporine Pharmacokinetics Nor With Cyclosporine Clinical End Points After Renal Transplantation.
Bouamar R, Hesselink DA, et al.Therapeutic Drug Monitoring, 33(2): 178-184, 2011.
Aims
This pharmacogenetic sub-study aimed to investigate the association between CYP3A4, CYP3A5, and ABCB1 single nucleotide polymorphisms (SNPs) and cyclosporine (CsA) pharmacokinetics as well as the influence of these genetic polymorphisms on the efficacy of CsA therapy and graft function after kidney transplantation.
Interventions
Mycophenolate mofetil (MMF) 1000 mg twice daily versus the MMF dose being adjusted on the basis of mycophenolic acid blood concentrations. All patients received either CsA or tacrolimus and glucocorticoids.
Participants
171 de novo kidney transplant recipients.
Outcomes
Incidence of biopsy-proven acute rejection, delayed graft function, patients and graft survival, and renal function. Cyclosporine pharmacokinetics parameters included pre-dose concentrations (C0) and 2 hours post-dose concentrations (C2). Genotype analysis included genotype of CYP3A4*1B, CYP3A5*3, ABCB1 1236C>T, 2677G>T/A and 3435C>T.
Follow-up
12 months
CET Conclusions
The 171 patients that were studied were participants in the international randomised controlled trial of fixed dose concentration versus controlled dose concentration (FDCC) trial. Relevant genotypes were studied prospectively but the results did not show that determination of CYP3A and ABCB1 SNPs pre-transplantation was helpful in allowing the starting dose of cyclosporine A to be determined and did not allow the risk of biopsy proven acute rejection or worse renal function to be determined in individual patients.
Data analysis
Strict intention-to-treat analysis
Quality notes
This is a subgroup analysis of a previous publication of the same RCT: van Gelder T, Silva HT, de Fijter JW, et al. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the Fixed-Dose Concentration-Controlled trial. Transplantation. 2008;86:1043–1051. The methodological quality assessment was based on the previous publication.
Trial registration
NCT00166244 (ClinicalTrials.gov)