Affiliation:
1. Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Abstract
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference24 articles.
1. Treatment of tuberculosis and tuberculosis infection in adults and children;American Thoracic Society/Centers for Disease Control.;Am. J. Respir. Crit. Care Med.,1994
2. 1983 Metropolitan height and weight tables;Anonymous;Stat. Bull. Metrop. Life Foundation,1983
3. Malabsorption of antituberculosis medications by an AIDS patient N;Berning S. E.;Engl. J. Med.,1992
4. Prediction of creatinine clearance from serum creatinine;Cockroft D. W.;Nephron,1976
5. D'Argenio D. and A. Schumitzky. 1992. ADAPT II user's guide biomedical simulations resource. University of Southern California Los Angeles.
Cited by
179 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献