Pharmacogenetic analysis of the absorption kinetics of cyclosporine in a population of Spanish cardiac transplant patients

Abstract

Objective

To determine how single nucleotide polymorphisms located on genes MDR1, CYP3A4, and CYP3A5 affect the absorption kinetics of cyclosporine in cardiac transplant patients.

Method

We selected a sample of 30 adult patients having previously undergone a primary cardiac transplant and who had received cyclosporine as an immunosuppressant. During the first month after the transplant, we performed a pharmacokinetic study of each patient to determine values in the cyclosporine concentration area under the 12-hour curve, steady-state cyclosporine concentration, maximum cyclosporine concentration, and time to reach that concentration. Single nucleotide polymorphisms were genotyped in all patients MDR1 3435C > T, CYP3A4-390A > G, and CYP3A5 6986A > G.

Results

Being a carrier of the T-allele for polymorphism MDR1 3435C > T is associated with higher values in the cyclosporine concentration area under the 12-hour curve (P=.01) and in steady-state cyclosporine concentration (P=.05), compared with those from patients who do not carry that allele.

Discussion

Our results show that genotype differences in MDR1 3435C > T can explain part of the variability in cyclosporine absorption among individuals in the population of Spanish cardiac transplant recipients.