Pharmacodynamics and Bactericidal Activity of Combination Regimens in Pulmonary Tuberculosis: Application to Bedaquiline-Pretomanid-Pyrazinamide.

ABSTRACT: A critical barrier to codevelopment of tuberculosis (TB) regimens is a limited ability to identify optimal drug and dose combinations in early-phase clinical testing. While pharmacokinetic-pharmacodynamic (PKPD) target attainment is the primary tool for exposure-response optimization of TB drugs, the PD target is a static index that does not distinguish individual drug contributions to the efficacy of a multidrug combination. A PKPD model of bedaquiline-pretomanid-pyrazinamide (BPaZ) for the treatment of pulmonary TB was developed as part of a dynamic exposure-response approach to regimen development. The model describes a time course relationship between the drug concentrations in plasma and their individual as well as their combined effect on sputum bacillary load assessed by solid cultu

SUBMITTER: Lyons MA 

PROVIDER: S-EPMC9765268 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature