Pharmacogenetics of Tacrolimus in Solid Organ Transplant Patients

Abstract

Tacrolimus is one of the most important immunosuppressant drugs used in organ transplants. The primary enzymes responsible for the metabolism of tacrolimus are cytochrome P450 3A4 and CYP3A5. Single nucleotide polymorphisms (SNPs) in the CYP3A4, CYP3A5, and ABCB1 genes, in particular, have been connected to changes in tacrolimus metabolism and clearance. Tacrolimus has a narrow therapeutic index and dose monitoring and adjustment are required.

Pharmacogenetic analyses have demonstrated that CYP3A5 genotypes account for a substantial amount of the variation in tacrolimus metabolism and clearance. Tacrolimus pharmacokinetics have also been widely studied in relation to ABCB1 polymorphisms, and some studies have demonstrated a notable impact on tacrolimus hepatic concentrations. Contradictory findings, however, have been documented, highlighting the necessity for more research in this field. In this manuscript, we compiled, reviewed, and discussed pharmacogenetic studies showing associations of genetic polymorphism with the efficacy and/or adverse effects of tacrolimus in solid organ transplant patients. We argue that knowledge of the function of genetic markers—specifically, SNPs in the CYP3A4, CYP3A5, and ABCB1 genes—is essential to maximizing the use of tacrolimus in clinical settings. This knowledge makes it possible to create customized treatment plans that will improve tacrolimus's effectiveness and safety for organ transplant recipients. Tacrolimus medication tailored to each patient based on genetic markers presents a viable way to enhance outcomes for organ transplant recipients. We recommend that tacrolimus dosage be customized to each patient's distinct genetic profile by identifying particular SNPs in the CYP3A4, CYP3A5, and ABCB1 genes. By doing this, the danger of side effects can be reduced and the drug's effectiveness can be maximized.