Effect of genetic polymorphism on clinical efficacy of Tacrolimus in adult living donor-liver transplant patients

Abstract

ransplantation literature includes numerous papers that report associations between polymorphisms in genes encoding metabolizing enzymes and drug transporters, and pharmacokinetic data on immunosuppressive drugs. Most of these studies are retrospective in design, and although a substantial number report significant associations, pharmacogenetic tests are hardly used in clinical practice. Individualized drug therapy with immunosuppressants is a hot topic in transplantation. Pharmacogenetics, by studying the relationship between a human genetic trait and drug disposition and response, holds great promises in optimizing immunosuppressive drug prescribing for solid organ transplantation. The calcineurin inhibitors ciclosporin (cyclosporine) and tacrolimus (TAC) are immunosuppressant drugs used for the prevention of organ rejection following transplantation. Patients using calcineurin inhibitors experience many adverse effects. In general, the number and severity of adverse effects are related to the overall exposure, measured by length of therapy and blood drug concentration. Both agents are metabolic substrates for cytochrome P450 (CYP) 3A enzymes - in particular, CYP3A4 and CYP3A5 - and are transported out of cells via P-glycoprotein.