Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin.

Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Research Abstract Details 

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Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Abstract Text:

Marc Weiner,William Burman,Chi-Cheng Luo,Charles A Peloquin,Melissa Engle,Stefan Goldberg,Vipin Agarwal,Andrew Vernon,

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 bioequivalence 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% CI, 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 mug.h/ml). Concomitant rifampin administration resulted in a 27% decrease in the mean moxifloxacin AUC(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.

Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Publishing Authors By Initials

M Weiner,W Burman,CC Luo,CA Peloquin,M Engle,S Goldberg,V Agarwal,A Vernon,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: therapeutic equivalency research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: therapeutic equivalency research

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Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Antimicrobial agents and chemotherapy

VOLUME: 51

Page Numbers: 2861-6

Journal Abbreviation: Antimicrob. Agents Chemother.

ISSN: 0066-4804

DAY: 21

MONTH: 05

YEAR: 2007

Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 315061

Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Keywords Mesh Terms:

KEYWORDS: Therapeutic Equivalency

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Information

Substance Name: Rifampin

Registry Number: 13292-46-1

Grant and Affiliation Information for Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin.

AFFILIATION: University of Texas Health Science Center, San Antonio and South Texas Veterans Health Care System, San Antonio, TX 78229-4404, USA. weiner@uthscsa.edu

Country: United States

AGENCY: United States NCRR

GRANT: M01 RR01346

ACRONYM: RR

MEDLINETA: Antimicrob Agents Chemother

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