Influence of CYP3A and ABCB1 Single Nucleotide Polymorphisms on the Pharmacokinetics/Pharmacodynamics of Tacrolimus in pediatric patients.

Single nucleotide polymorphisms (SNPs) are the most common variants in many genes, which are also promising markers in relation to drug responses in pharmacogenomics studies. Tacrolimus is a primary immunosuppressant used for the prevention of organ rejection in pediatric organ transplantation. Tacrolimus, transported out of cells via P-glycoprotein (ABCB1), is also a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, especially the CYP3A4 and the CYP3A5. The SNP of these genes have been studied extensively in adult population, but there is no systematic review in children. In this paper, we focus on the impact of CYP3A and ABCB1 SNPs on tacrolimus in children undergoing organ transplantations. Literature searches were performed and all relevant primary research articles were critiqued and summarized. There is no evidence that the CYP3A4 SNP has an effect on the pharmacokinetics/pharmacodynamics of tacrolimus in children. And, the majority of studies have failed to find an association between the ABCB1 SNP and pharmacokinetics of tacrolimus in children. However, although the amount of literature is limited, it does show an association between ABCB1 SNPs and pharmacodynamics of tacrolimus. Despite a strong association between CYP3A5 SNP and tacrolimus pharmacokinetics has been demonstrated, there is no direct evidence to prove the effect of CYP3A5 SNP on pharmacodynamics of tacrolimus. More standardized clinical trials are needed to evaluate the relationship between the CYP3A5 SNP and the pharmacodynamics of tacrolimus, particularly in regard to the outcomes of acute rejection and nephrotoxicity.