Rifampicin population pharmacokinetics and pharmacogenomic evaluation of SLCO1B1 gene in tuberculosis patients.
Avinash Lomash, Vandana Roy, Shilpa Daniel, Syed Shariq Naeem, Seema Kapoor, Ashwani Khanna, Mradul Kumar Daga
The Indian journal of tuberculosis · 2026-04
Abstract
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 (C) was 9.34 μg/ml at Tof 2.15 h. Mean AUCwas 42.2 μg/ml. In 16.6 % cases, Cwas <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 C<8 μg/ml. No significance of covariates on PopPK and correlation between RMP Clevels 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.
MeSH terms
- Humans
- Rifampin
- Liver-Specific Organic Anion Transporter 1
- Male
- Female
- Adult
- Antibiotics, Antitubercular
- Middle Aged
- Tuberculosis
- Young Adult
- Polymorphism, Single Nucleotide
- Genotype