Pretomanid dose selection for pulmonary tuberculosis: An application of multi-objective optimization to dosage regimen design.

ABSTRACT: Clinical development of combination chemotherapies for tuberculosis (TB) is complicated by partial or restricted phase II dose-finding. Barriers include a propensity for drug resistance with monotherapy, practical limits on numbers of treatment arms for component dose combinations, and limited application of current dose selection methods to multidrug regimens. A multi-objective optimization approach to dose selection was developed as a conceptual and computational framework for currently evolving approaches to clinical testing of novel TB regimens. Pharmacokinetic-pharmacodynamic (PK-PD) modeling was combined with an evolutionary algorithm to identify dosage regimens that yield optimal trade-offs between multiple conflicting therapeutic objectives. The phase IIa studies for pretomanid, a

SUBMITTER: Lyons MA 

PROVIDER: S-EPMC7965837 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature