Investigation of clinical interaction between omeprazole and tacrolimus in CYP3A5 non-expressors, renal transplant recipients

Abstract

As proton pump inhibitors share CYP3A4 enzyme with tacrolimus for their hepatic elimination, they potentially affect its pharmacokinetics, most prominently in patients with CYP2C19 or CYP3A5 gene mutations. Our aim was to investigate the impact of omeprazole on tacrolimus pharmacokinetics in CYP3A5 non-expressors, kidney transplant recipients. Twelve patients (five males/seven females) were observed for 175 +/- 92.05 days. Omeprazole (20 mg pos) was administrated for 75.83 +/- 45.17 days. Immunosuppressant regimen consisted of tacrolimus (n = 12), methylprednisolone (n = 10), mycophenolate mofetil (n = 11), azathioprine (n = 1), and everolimus (n = 2). Patient's body weight, coadministered drugs, and tacrolimus trough levels were monitored. Aspartate and alanine aminotransferase, gamma-glutamyltransferase, and bilirubin were used for evaluating hepatic function. Tacrolimus kinetics were estimated with daily dose, concentration, dose adjusted concentration, and volume of distribution with and without coadministration of omeprazole. CYP3A5 genotyping was performed with PCR followed by restriction fragment length polymorphism analysis. Statistical analysis was performed with Prism 4 software (GraphPad Software, Inc). No statistically significant difference was observed in tacrolimus kinetics and hepatic function during coadministration of omeprazole. Our results let us propose that there is no need for more frequent therapeutic drug monitoring of tacrolimus when coadministrated with omeprazole in CYP3A5 nonexpressors, though prospective studies with more patients and longer observation period are needed to confirm these findings.