Comparative Efficacy of Rifapentine Alone and in Combination with Isoniazid for Latent Tuberculosis Infection: a Translational Pharmacokinetic-Pharmacodynamic Modeling Study.

ABSTRACT: Rifapentine has facilitated treatment shortening for latent tuberculosis infection (LTBI) in combination with isoniazid once weekly for 3 months (3HP) or daily for 1 month (1HP). Our objective was to determine the optimal rifapentine dose for a 6-week monotherapy regimen (6wP) and predict clinical efficacy. Rifapentine and isoniazid pharmacokinetics were simulated in mice and humans. Mouse lung CFU data were used to characterize exposure-response relationships of 1HP, 3HP, and 6wP and translated to predict clinical efficacy. A 600-mg daily dose for 6wP delivered greater cumulative rifapentine exposure than 1HP or 3HP. The maximum regimen effect (E_max) was 0.24 day^-1. The regimen potencies, measured as the concentration at 50% of E_max (EC₅

SUBMITTER: Radtke KK 

PROVIDER: S-EPMC8597776 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature