A New Functional CYP3A4 Intron 6 Polymorphism Significantly Affects Tacrolimus Pharmacokinetics in Kidney Transplant Recipients.
Elens L. Bouamar R. et al.Clinical Chemistry. 57(11): 1574-1583, 2011.
Aims
To explore whether the new CYP3A4 single nucleotide polymorphism correlates with reduced clearance of tacrolimus and thus might predict lower dose requirements of tacrolimus in kidney transplant recipients.
Interventions
Cyclosporine A (CsA) conversion to sirolimus (SRL) treatment at 3 months after transplantation versus continuation of CsA treatment in combination with mycophenolate mofetil.
Participants
185 renal transplant recipients.
Outcomes
Biopsy-proven acute rejection (BPAR) and delayed graft function, which was defined as a need for dialysis within the first week after transplantation. Pharmacokinetic parameters included C0 measurement on days 3 and 10, and at months 1, 3, 6, and 12 after transplantation. Genotype analysis included CYP3A5*3 analysis and ABCB1 1236C>T, 2677G>T/A, and 3435C>T analyses.
Follow-up
12 months
CET Conclusions
The newly discovered CYP3A4 single nucleotide polymorphism was shown in patients participating in an international randomised controlled trial to significantly influence the metabolism of tacrolimus. In its presence there was a reduced clearance of tacrolimus and a considerable reduction of tacrolimus doses was possible. The definition of this polymorphism in transplant patients, along with CYP3A5*3, could benefit patients by not only allowing reduction of initial doses of tacrolimus but also decreasing the risk of supratherapeutic concentrations of tacrolimus when these CYP3A alleles are expressed.
Data analysis
Strict intention-to-treat analysis
Quality notes
This is a substudy of an original publication: van Gelder T, Silva HT, de Fijter JW, Budde K,Kuypers D, Tyden G, et al. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration controlled trial. Transplantation 2008;86:1043–51. The quality assessment was based on the original publication.
Trial registration
Not reported