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Antimicrobial Agents and Chemotherapy, August 2007, p. 2861-2866, Vol. 51, No. 8
0066-4804/07/$08.00+0     doi:10.1128/AAC.01621-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Effects of Rifampin and Multidrug Resistance Gene Polymorphism on Concentrations of Moxifloxacin{triangledown}

Marc Weiner,1* William Burman,2 Chi-Cheng Luo,3 Charles A. Peloquin,4 Melissa Engle,1 Stefan Goldberg,3 Vipin Agarwal,5 and Andrew Vernon3

University of Texas Health Science Center San Antonio and South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, Texas 78229-4404,1 Denver Public Health, 605 Bannock Street, Denver, Colorado 80204,2 Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, 1600 Clifton Rd., NE, Atlanta, Georgia 30333,3 National Jewish Medical, 1400 Jackson St., Denver, Colorado 80206,4 NorthEast Bioanalytical Laboratories, 925 Sherman Ave., Hamden, Connecticut5

Received 28 December 2006/ Returned for modification 2 March 2007/ Accepted 15 May 2007

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 (AUC0-24) for moxifloxacin decreased 27%. Average bioequivalence between moxifloxacin coadministered with rifampin and moxifloxacin alone was not demonstrated: the ratio of geometric means (RGM) of the moxifloxacin AUC0-24 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% CI, 80.2, 109.3) (total P value, 0.049). Concentrations of the sulfate conjugate metabolite of moxifloxacin were increased twofold following rifampin coadministration (AUC0-24, 1.29 versus 2.79 µg·h/ml). Concomitant rifampin administration resulted in a 27% decrease in the mean moxifloxacin AUC0-24 and a marked increase in the AUC0-24 of the microbiologically inactive M1 metabolite. Additional studies are required to understand the clinical significance of the moxifloxacin-rifampin interaction.

* Corresponding author. Mailing address: VAMC, Division Infectious Diseases (111F), 7400 Merton Minter Blvd., San Antonio, TX 78229-4404. Phone: (210) 617-5300, ext. 16060. Fax: (210) 617-5297. E-mail: weiner{at}uthscsa.edu

{triangledown} Published ahead of print on 21 May 2007.

Antimicrobial Agents and Chemotherapy, August 2007, p. 2861-2866, Vol. 51, No. 8
0066-4804/07/$08.00+0     doi:10.1128/AAC.01621-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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