Effect of food on the pharmacokinetics of rifalazil, a novel antibacterial, in healthy male volunteers

Abstract

Background This study investigated the safety and pharmacokinetics of a single 25 mg dose of rifalazil, a new antibiotic related to rifampin, administered under three dietary regimens to healthy male volunteers. Methods In a Phase I, randomized, three-way crossover, single oral dose study of rifalazil, healthy male volunteers (N=11) received three single 25 mg oral doses of rifalazil under three conditions (standard breakfast, high-fat breakfast, or overnight fast of 10 hours) with a 21–28 day washout between each dose. Plasma samples were assayed by LC/MS/MS. PK analysis was determined by nonlinear regression methods employing a two-compartmental open model. Results Systemic exposure to rifalazil based on Cmax and AUC were increased progressively and results were statistically significant as the fat content of the test breakfast was increased from 30 to 60% of calories compared with fasting. This positive food effect may be a result of increased fractional absorption with increasing dietary fat content. Conclusions Rifalazil was well tolerated. Food significantly increased rifalazil's systemic exposure and was further enhanced by the percentage of dietary fat content. Clinical Pharmacology & Therapeutics (2005) 77, P44–P44; doi: 10.1016/j.clpt.2004.12.061