Search: onr:"swepub:oai:DiVA.org:uu-23901" >
Variability in the ...
Variability in the population pharmacokinetics of pyrazinamide in South African tuberculosis patients
-
- Wilkins, Justin J. (author)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi
-
- Langdon, Grant (author)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi
-
McIlleron, Helen (author)
-
show more...
-
Pillai, Goonaseelan Colin (author)
-
Smith, Peter J. (author)
-
- Simonsson, Ulrika S. H. (author)
- Uppsala universitet,Avdelningen för farmakokinetik och läkemedelsterapi
-
show less...
-
(creator_code:org_t)
- 2006-05-10
- 2006
- English.
-
In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 62:9, s. 727-735
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- interoccasional variability
- interindividual variability
- pyrazinamide
- tuberculosis
- PHARMACY
- FARMACI
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database