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.