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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Population pharmacokinetics and pharmacodynamics of ofloxacin in South African patients with multidrug-resistant tuberculosis
Antimicrobial Agents and Chemotherapy, Volume 56, No. 7, Year 2012
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Description
Despite the important role of fluoroquinolones and the predominant use of ofloxacin for treating multidrug-resistant tuberculosis in South Africa, there are limited data on ofloxacin pharmacokinetics in patients with multidrug-resistant tuberculosis, no ofloxacin pharmacokinetic data from South African patients, and no direct assessment of the relationship between ofloxacin pharmacokinetics and the MIC of ofloxacin of patient isolates. Our objectives are to describe ofloxacin pharmacokinetics in South African patients being treated for multidrug-resistant tuberculosis and assess the adequacy of ofloxacin drug exposure with respect to the probability of pharmacodynamic target attainment (area under the time curve/MIC ratio of at least 100). Sixty-five patients with multidrug-resistant tuberculosis were recruited from 2 hospitals in South Africa. We determined the ofloxacin MICs for the Mycobacterium tuberculosis isolates from baseline sputum specimens. Patients received daily doses of 800 mg ofloxacin, in addition to other antitubercular drugs. Patients underwent pharmacokinetic sampling at steady state. NONMEM was used for data analysis. The population pharmacokinetics of ofloxacin in this study has been adequately described. The probability of target attainment expectation in the study population was 0.45. Doubling the dose to 1,600 mg could increase this to only 0.77. The currently recommended ofloxacin dose appeared inadequate for the majority of this study population. Studies to assess the tolerability of higher doses are warranted. Alternatively, ofloxacin should be replaced with more potent fluoroquinolones. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Chigutsa, Emmanuel
South Africa, Cape Town
University of Cape Town
Meredith, Sandra A.
South Africa, Cape Town
University of Cape Town
Wiesner, L. D.
South Africa, Cape Town
University of Cape Town
Padayatchi, Nesri
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Harding, Joseph
South Africa, Cape Town
Dp Marais Hospital
Moodley, Prashini
South Africa, Durban
College of Health Sciences
Kenzie, William R.Mac
United States, Atlanta
Centers for Disease Control and Prevention
Weiner, Marc H.
South Africa, Durban
Tbtc Study 30 Team
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
Kirkpatrick, Carl M.J.
Australia, Clayton
Monash University
Statistics
Citations: 32
Authors: 10
Affiliations: 7
Identifiers
Doi:
10.1128/AAC.00048-12
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Health System And Policy
Study Design
Cross Sectional Study
Study Locations
South Africa