Rifampin, a member of the rifamycin class of antibiotics, is well known for its ability to activate the pregnant X receptor and induce drug-metabolizing enzymes and transporters. Available data suggest rifampin entry into hepatocytes is mediated by OATP1B1. Accordingly, it is therefore plausible that modulation of the intracellular concentration of rifampin by OATP1B1 genetic polymorphisms would influence the degree of CYP3A induction. AIM: To study the association between haplotypes of the SLCO1B1 and the rifampicin-mediated inducible CYP3A4 activity. A single-point determination of midazolam plasma concentration method was developed to assess the constitutive and inducible CYP3A4 activity. A pharmacokinetic study of a single dose of 450 mg rifampicin was conducted to evaluate the mechanism of rifampicin-midazolam interaction in different SLCO1B1 genotypic subjects. METHODS: Twenty-three healthy volunteers with different SLCO1B1 haplotypes (7 for SLCO1B1*1a/*1a, 7 for SLCO1B1*1b/*1b, 7 for SLCO1B1*1b/*15 and 2 for SLCO1B1*15/*15) were enrolled in this study. Each was given a single oral dose of 7.5 mg midazolam on day 0 and day 6. Rifampicin of 450 mg was given from day 1 to day 5. Plasma concentrations of midazolam were measured for up to 8 hours by LC-MS, and its pharmacokinetic parameters were analyzed. Plasma concentrations of a single oral dose of 450 mg rifampicin were measured for up to 12 hours. RESULTS: A significant correlation (r2=0.763, P<0.001, n=23) was found between AUC(0-∞) and the single plasma concentration of midazolam at 2.5 hour (C2.5 h). The 2.5 h midazolam measurement was an optimal predictor of CYP3A phenotype. However, the percentage reduction of AUC(0-∞) or C2.5 h in different SLCO1B1 haplotypes was not significantly different. The pharmacokinetics parameters of rifampin were not significantly different between the 521T>C mutant group and the control group. CONCLUSION: A single blood concentration at 2.5 h after 7.5 mg oral midazolam intake can be used to predict CYP3A activity. The SLCO1B1 haplotypes do not influence the extent of inducible CYP3A activity by rifampin. SLCO1B1 genotypes has no significant impact on the disposition of rifampin in vivo. Rifampin, a member of the rifamycin class of antibiotics, is well known for its ability to activate the pregnant X receptor and induce drug-metabolizing enzymes and transporters. Available data suggest rifampin entry into hepatocytes is mediated by OATP1B1. that modulation of the intracellular concentration of rifampin by OATP1B1 genetic polymorphisms would influence the degree of CYP3A induction. AIM: To study the association between haplotypes of the SLCO1B1 and the rifampicin-mediated inducible CYP3A4 activity. A single-point determination of midazolam plasma concentration method was developed to assess the constitutive and inducible CYP3A4 activity. A pharmacokinetic study of a single dose of 450 mg rifampicin was conducted to evaluate the mechanism of rifampicin-midazolam interaction in different SLCO1B1 genotypic subjects. METHODS: Twenty-three healthy volunteers with different SLCO1B1 haplotypes (7 for SLCO1B1 * 1a / * 1a, 7 for SLCO1B1 * 1b / * 1b, 7 for SLCO1B1 * 1b / * 15 and 2 for SLCO1B1 * 15 / * 15) were enrolled in this study. Each was given a single oral dose of 7.5 mg midazolam on day 0 and day 6. Rifampicin of 450 mg was given from day 1 to day 5. Plasma concentrations of midazolam were measured for up to 8 hours by LC-MS, and its pharmacokinetic parameters were analyzed. Plasma concentrations of a single oral dose of 450 mg rifampicin were measured for up to 12 hours. Significant correlation (r2 = 0.763, P <0.001, n = 23) was found between AUC (0-∞) and single plasma concentration of midazolam at 2.5 hour (C2.5 h). The 2.5 h midazolam measurement was an optimal predictor of CYP3A phenotype. However, the percentage reduction of AUC (0-∞) or C2.5 h in different SLCO1B1 haplotypes was not significantly different. The pharmacokinetics parameters of rifampin were not significantly different between the 521T> C mutant group and the control group CONCLUSION: A single blood concentration at 2.5 h after 7.5 mg oral midazolam i ntakThe SLCO1B1 haplotypes do not influence the extent of inducible CYP3A activity by rifampin. SLCO1B1 genotypes has no significant impact on the disposition of rifampin in vivo.