Double-Blind, Randomized, Placebo-Controlled Phase II Dose-Finding Study To Evaluate High-Dose Rifampin for Tuberculous Meningitis.

ABSTRACT: High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13?mg/kg given intravenously or 20?mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450?mg, 900?mg, or 1,350?mg (10, 20, and 30?mg/kg) oral rifampin combined with other TB drugs for 30?days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2?±?1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0-24], 53.5?mg?·?h/liter versus 170.6?mg?·?h/liter and 293.5?mg?·?h/liter, respectively; P?

SUBMITTER: Dian S 

PROVIDER: S-EPMC6256787 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature