Rifampicin population pharmacokinetics and pharmacogenomic evaluation of SLCO1B1 gene in tuberculosis patients.

BACKGROUND

Rifampicin (RMP) is a key drug in the standard anti-tubercular regime. Variations in the SLCO1B1 gene are reported to influence RMP blood levels in tuberculosis patients. Association between SLCO1B1 gene and RMP concentration in tuberculosis patients was evaluated.

METHOD: RMP blood levels were determined at 0,1, 2,3,4,6,8,12 h after administration in 72 patients. Population pharmacokinetic (PopPK) and SLCO1B1 gene variations were analyzed.

RESULTS

Peak RMP concentration (Cmax) was 9.34 μg/ml at Tmax of 2.15 h. Mean AUC0-12 was 42.2 μg/ml. In 16.6 % cases, Cmax was <8 μg/ml with higher (10.01 L/h) clearance. Covariates effect depicted that out of 13, one compartment with first order absorption and linear elimination with Tlag was the best fit. Majority of GA (65 %) and GG (23 %) alleles of 388A > G genotype were observed in patients with Cmax<8 μg/ml. No significance of covariates on PopPK and correlation between RMP Cmax levels and 463C > A polymorphism was observed. Lower RMP levels were observed with GA and GG alleles of 388A > G genotype.

CONCLUSIONS

A total of 16.6 % cases depicted peak RMP Cmax<8 μg/ml with higher clearance. No association between RMP levels and 463C > A polymorphism was observed. However, 388A > G polymorphism affects RMP absorption in blood.