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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Effects of four different meal types on the population pharmacokinetics of single-dose rifapentine in healthy male volunteers
Antimicrobial Agents and Chemotherapy, Volume 54, No. 8, Year 2010
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Description
Rifapentine and its primary metabolite, 25-desacetyl rifapentine, are active against mycobacterium tuberculosis. The objectives of this study were to describe the population pharmacokinetics of rifapentine and 25-desacetyl rifapentine in fasting and fed states. Thirty-five male healthy volunteers were enrolled in an open-label, randomized, sequential, five-way crossover study. Participants received a single 900-mg dose of rifapentine after meals with high fat (meal A), bulk and low fat (meal B), bulk and high fat (meal C), high fluid and low fat (meal D), or 200 ml of water (meal E). Venous blood samples were collected over 72 h after each rifapentine dose, and plasma was analyzed for rifapentine and 25-desacetyl rifapentine using high-performance liquid chromatography. Pharmacokinetic data were analyzed by nonlinear mixed-effect modeling using NONMEM. Compared with the fasting state, meal A had the greatest effect on rifapentine oral bioavailability, increasing it by 86%. Meals B, C, and D resulted in 33%, 46%, and 49% increases in rifapentine oral bioavailability, respectively. Similar trends were observed for 25-desacetyl rifapentine. As meal behavior has a substantial impact on rifapentine exposure, it should be considered in the evaluation of optimal dosing approaches. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Zvada, Simbarashe Peter
South Africa, Cape Town
University of Cape Town
van der Walt, Jan Stefan
South Africa, Cape Town
University of Cape Town
Sweden, Uppsala
Uppsala Universitet
Smith, Peter John
South Africa, Cape Town
University of Cape Town
Fourie, P. B.
South Africa, Pretoria
Medicine in Need South Africa
Roscigno, Giorgio
Switzerland, Geneva
Foundation for Innovative new Diagnostics, Switzerland
Mitchison, Dennis Anthony
United Kingdom, London
St George’s, University of London
Simonsson, Ulrika S.H.
Sweden, Uppsala
Uppsala Universitet
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 36
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1128/AAC.00345-10
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Environmental
Health System And Policy
Study Design
Cross Sectional Study
Participants Gender
Male