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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Variability in the population pharmacokinetics of pyrazinamide in South African tuberculosis patients
European Journal of Clinical Pharmacology, Volume 62, No. 9, Year 2006
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Description
Objective: This study was designed to characterize the population pharmacokinetics of pyrazinamide in South African pulmonary tuberculosis patients, with special reference to interindividual and interoccasional variability (IIV and IOV, respectively). Methods: Concentration-time measurements obtained from 227 patients receiving oral doses of pyrazinamide were pooled to create a dataset containing 3,092 data points spanning multiple dosing occasions. The software program NONMEM was used to analyze the data. Results: A one-compartment model with first-order absorption, including a zero-order component describing release from formulation, and first-order elimination best described the data. The absorption rate constant was estimated to be bimodally distributed between two distinct subgroups, fast and slow, in approximately even proportion. Absorption rate was threefold greater in fast absorbers (3.56 h-1) in comparison to slow absorbers (1.25 h -1). Typical values of oral clearance and apparent volume of distribution were estimated as 3.42 L h-1 and 29.2 l, respectively. IOV was supported in oral clearance (0.0238, variance) and absorption rate (0.623, variance). The duration of zero-order absorption was estimated as 0.290 h, and was quite variable between patients (0.957, variance). Conclusion: The absorption of pyrazinamide in the studied population was highly variable and two separate subpopulations were identified. IOV accounted for a proportion of the variability in clearance and the absorption rate constant. © Springer-Verlag 2006.
Authors & Co-Authors
Wilkins, Justin J.
South Africa, Cape Town
University of Cape Town
Sweden, Uppsala
Uppsala Universitet
Langdon, Grant
South Africa, Cape Town
University of Cape Town
Sweden, Uppsala
Uppsala Universitet
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
South Africa, Observatory
Groote Schuur Hospital
Pillai, Goonaseelan ‘Colin’
Switzerland, Basel
Novartis International ag
Smith, Peter J.D.
South Africa, Cape Town
University of Cape Town
Simonsson, Ulrika S.H.
Sweden, Uppsala
Uppsala Universitet
Statistics
Citations: 80
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1007/s00228-006-0141-z
Research Areas
Health System And Policy
Study Design
Cross Sectional Study