Factors associated with variability in rifampin plasma pharmacokinetics and the relationship between rifampin concentrations and induction of efavirenz clearance.

摘要: Rifampin is an essential component of short-course chemotherapy for tuberculosis (TB).1 Findings from randomized clinical studies demonstrate that the addition rifampin to treatment regimens during induction and continuation phases TB reduce rates failure relapse.2,3 In vitro suggest demonstrates concentration-dependent killing Mycobacterium tuberculosis, with area under concentration-time curve (AUC) minimum inhibitory concentration (MIC) ratio identified as best parameter correlated reduction in bacterial counts.4, 5 hollow-fiber model TB, maximal microbial was achieved by daily AUC0-24h/MIC 24.14 prevented resistance itself at peak (Cmax) MIC ≥ 175.4 Clinically, low plasma exposure rifamycins has been associated emergence rifamycin resistance.6-8 The organic anion transporter polypeptide 1B1 (OATP1B1) encoded solute carrier family member (SLCO1B1) gene mediates hepatic uptake elimination a range drugs, including rifampin.9 Data recent show SLCO1B1 c.463C→A rs4149032 polymorphisms are concentrations.10, 11 While these findings novel, they yet be replicated or confirmed other studies. Taken together, genetic testing information may used identify patients risk could enable individualized dosing designed optimize outcomes. Concomitant administration efavirenz-containing antiretroviral therapy HIV co-infected necessary mortality rates.12-14 potent inducer cytochrome P450 enzyme activity, concomitant efavirenz results reduced concentrations some, but not all patients.15-17 variable effect on pharmacokinetics due, part, inter-individual variations into hepatocytes, this hypothesis previously evaluated, our knowledge. Using stored samples data subjects previous drug-drug interaction study,16 we sought factors pharmacokinetics. addition, explored relationship between change clearance.