Modeling and Simulation of Pretomanid Pharmacodynamics in Pulmonary Tuberculosis Patients.

ABSTRACT: Pretomanid (PA-824) is a nitroimidazole in clinical testing for the treatment of tuberculosis. A population pharmacodynamic model for pretomanid was developed using a Bayesian analysis of efficacy data from two early bactericidal activity (EBA) studies, PA-824-CL-007 and PA-824-CL-010, conducted in Cape Town, South Africa. The two studies included 122 adult male and female participants with newly diagnosed pulmonary tuberculosis who received once daily oral pretomanid doses of either 50, 100, 150, 200, 600, 1,000, or 1,200 mg for 14 days. The structural model described capacity-limited growth and saturable drug-induced bacterial killing with separate rate equations for sputum solid culture colony forming unit (CFU) counts and liquid culture time to positivity (TTP) that were linked through

SUBMITTER: Lyons MA 

PROVIDER: S-EPMC6879235 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature