Pharmacy and Pharmaceutical Sciences Commons^™

Beyond Single Nucleotide Polymorphisms: Cyp3a5∗3 ∗6 ∗7 Composite And Abcb1 Haplotype Associations To Tacrolimus Pharmacokinetics In Black And White Renal Transplant Recipients, Daniel A. Brazeau, Kristopher Attwood, Calvin J. Meaney, Gregory E. Wilding, Joseph D. Consiglio, Shirley S. Chang, Aijaz Gundroo, Rocco C. Venuto, Louise Cooper, Kathleen M. Tornatore

Pharmaceutical Science and Research

Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A5 (CYP3A5) isoenzymes and membrane transport by P-glycoprotein. Interpatient pharmacokinetic variability has been associated with genotypic variants for both CYP3A5 or ABCB1. Tacrolimus pharmacokinetics was investigated in 65 stable Black and Caucasian post-renal transplant patients by assessing the effects of multiple alleles in both CYP3A5 and ABCB1. A metabolic composite based upon the CYP3A5 polymorphisms: ^∗3(rs776746), ^∗6(10264272), and ^∗7(41303343), each independently responsible for loss of protein expression was used to classify patients as extensive, intermediate and poor metabolizers. In addition, the …