期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 51, 期 8, 页码 2861-2866出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01621-06
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资金
- NCRR NIH HHS [M01 RR01346, M01 RR001346] Funding Source: Medline
Treatment regimens combining moxifloxacin and rifampin for drug-susceptible tuberculosis are being studied intensively. However, rifampin induces enzymes that transport and metabolize moxifloxacin. We evaluated the effect of rifampin and the human multidrug resistance gene (MDR1) C3435T polymorphisms (P-glycoprotein) on moxifloxacin pharmacokinetic parameters. This was a single-center, sequential design study with 16 volunteers in which sampling was performed after four daily oral doses of moxifloxacin (400 mg) and again after 10 days of combined rifampin (600 mg) and moxifloxacin. After daily coadministration of rifampin, the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) for moxifloxacin decreased 27%. Average bioequivallence between moxifloxacin coadministered with rifampin and moxifloxacin alone was not demonstrated: the ratio of geometric means (RGM) of the moxifloxacin AUC(0-24) was 73.3 (90% confidence intervals [CI], 64.3, 83.5) (total P value, 0.87 for two one-sided t tests). Peak moxifloxacin concentrations, however, were equivalent: the RGM of the maximum concentration of the drug in serum was 93.6 (90% Cl, 80.2, 109.3) (total P value, 0.049). Concentrations of the sulfate conjugate metabolite of moxifloxacin were increased twofold following rifampin coadministration (AUC(0-24), 1.29 versus 2.79 mu g - h/ml). Concomitant rifampin administration resulted in a 27% decrease in the mean moxifloxacin AU(0-24),-,, and a marked increase in the AUC(0-24),, of the microbiologically inactive M1 metabolite. Additional studies are required to understand the clinical significance of the moxifloxacin-rifampin interaction.
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