Title
Prevention of drug carryover effects in studies assessing antimycobacterial efficacy of TMC207 Prevention of drug carryover effects in studies assessing antimycobacterial efficacy of TMC207
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Washington, D.C. ,
Subject
Pharmacology. Therapy
Source (journal)
Journal of clinical microbiology. - Washington, D.C.
Volume/pages
46(2008) :7 , p. 2212-2215
ISSN
0095-1137
ISI
000258906800011
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The levels of TMC207 (R207910) that can be reached in mouse organs and the sputa of treated patients easily exceed the MIC of the compound and can therefore interfere with in vitro bacterial titrations. We studied the usefulness of protein-enriched media for the prevention of such drug carryover effects. The average MIC of Mycobacterium tuberculosis was determined on three different media: unsupplemented 7H11 agar (MIC = 0.03 µg/ml), 7H11 agar supplemented with 5% bovine serum albumin (BSA; MIC = 1 µg/ml), and Lowenstein-Jensen medium (MIC = 14.33 µg/ml). In a second stage of the study, the maximal noninhibitory concentrations (MNICs) of TMC207 were determined by adding TMC207 to the bacterial inoculum rather than to the culture medium. These MNICs were 0.97 µg/ml for 7H11 agar, 32.33 µg/ml for 7H11 agar with 5% BSA, and 96.33 µg/ml for Lowenstein-Jensen medium. Both protein-enriched media were able to prevent drug carryover effects, but the use of 7H11 medium supplemented with 5% BSA is preferred for practical reasons.
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