Effect of rifampicin & isoniazid on the steady state pharmacokinetics of moxifloxacin

BACKGROUND & OBJECTIVES: Moxifloxacin (MFX) is reported to have promising antimycobacterial activity, and has a potential to shorten tuberculosis (TB) treatment. We undertook this study to examine the influence of rifampicin (RMP) and isoniazid (INH) on the steady state pharmacokinetics of MFX individually in healthy individuals. METHODS: A baseline pharmacokinetic study of MFX (400 mg once daily) was conducted in 36 healthy adults and repeated after one week of daily MFX with either RMP (450/600 mg) (n = 18) or INH (300 mg) (n = 18). Plasma MFX concentrations were determined by a validated HPLC method. RESULTS: Plasma peak concentration and exposure of MFX was significantly lower and plasma clearance significantly higher when combined with RMP (P<0.001). The C(max) to MIC and AUC(0-12) to MIC ratios of MFX were significantly lower during concomitant RMP (P<0.001). INH had no significant effect on the pharmacokinetics of MFX. INTERPRETATION & CONCLUSIONS: Concomitant RMP administration caused a significant decrease in C(max) and AUC(0-12) of MFX, the mean decreases being 26 and 29 per cent, respectively. It is uncertain whether this decrease would affect the treatment efficacy of MFX. Prospective studies in TB patients are needed to correlate MFX pharmacokinetics with treatment outcomes.