| Population pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide. | |
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MedLine Citation:
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PMID: 9420037 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) are the most important drugs for the treatment of tuberculosis (TB). The pharmacokinetics of all three drugs in the plasma of 24 healthy males were studied as part of a randomized cross-over phase I study of two dosage forms. Subjects ingested single doses of INH at 250 mg, RIF at 600 mg, and PZA at 1,500 mg. Plasma was collected for 36 h and was assayed by high-performance liquid chromatography. The data were analyzed by noncompartmental, iterative two-stage maximum a posteriori probability Bayesian (IT2B) and nonparametric expectation maximization (NPEM) population modeling methods. Fast and slow acetylators of INH had median peak concentrations in plasma (C[max]) of 2.44 and 3.64 microg/ml, respectively, both of which occurred at 1.0 h postdose (time of maximum concentrations of drugs in plasma [T(max)]), with median elimination half-lives (t1/2) of 1.2 and 3.3 h, respectively (by the NPEM method). RIF produced a median C(max) of 11.80 microg/ml, a T(max) of 1.0 h, and a t1/2 of 3.4 h. PZA produced a median C(max) of 28.80 microg/ml, a T(max) of 1.0 h, and a t1/2 of 10.0 h. The pharmacokinetic behaviors of INH, RIF, and PZA were well described by the three methods used. These models can serve as benchmarks for comparison with models for other populations, such as patients with TB or TB with AIDS. |
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Authors:
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C A Peloquin; G S Jaresko; C L Yong; A C Keung; A E Bulpitt; R W Jelliffe |
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Publication Detail:
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Type: Clinical Trial; Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 41 ISSN: 0066-4804 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 1997 Dec |
Date Detail:
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Created Date: 1998-01-29 Completed Date: 1998-01-29 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2670-9 Citation Subset: IM; X |
Affiliation:
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Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Absorption Adult Analysis of Variance Antibiotics, Antitubercular / blood, pharmacokinetics* Antitubercular Agents / blood, pharmacokinetics* Chromatography, High Pressure Liquid Cross-Over Studies Dose-Response Relationship, Drug Humans Isoniazid / blood, pharmacokinetics* Male Middle Aged Pyrazinamide / blood, pharmacokinetics* Rifampin / blood, pharmacokinetics* |
| Grant Support | |
ID/Acronym/Agency:
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LM 05401/LM/NLM NIH HHS; R01 AI37845/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antitubercular; 0/Antitubercular Agents; 13292-46-1/Rifampin; 54-85-3/Isoniazid; 98-96-4/Pyrazinamide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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