Role of vitamin D pathway gene polymorphisms on rifampicin plasma and intracellular pharmacokinetics

Abstract

Aim: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations. Patients & methods: Rifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography–tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction. Results: Twenty-four patients were enrolled. At week 2, OATP1B1 521TT and CYP27B1 +2838CC/CT considering plasma and BsmIAA for intraperipheral blood mononuclear cells Cmax, remained in regression analysis. Concerning week 4, TaqITC/CC and CYP24A1 22776CT/TT were retained in plasma Cmax regression model. Conclusion: This study confirms the role of SLCO1B1 and it suggests the involvement of vitamin D pathway gene polymorphisms in rifampicin pharmacokinetics.