Assessing Pharmacodynamic Interactions in Mice Using the Multistate Tuberculosis Pharmacometric and General Pharmacodynamic Interaction Models.

ABSTRACT: The aim of this study was to investigate pharmacodynamic (PD) interactions in mice infected with Mycobacterium tuberculosis using population pharmacokinetics (PKs), the Multistate Tuberculosis Pharmacometric (MTP) model, and the General Pharmacodynamic Interaction (GPDI) model. Rifampicin, isoniazid, ethambutol, or pyrazinamide were administered in monotherapy for 4 weeks. Rifampicin and isoniazid showed effects in monotherapy, whereas the animals became moribund after 7 days with ethambutol or pyrazinamide alone. No PD interactions were observed against fast-multiplying bacteria. Interactions between rifampicin and isoniazid on killing slow and non-multiplying bacteria were identified, which led to an increase of 0.86 log₁₀ colony-forming unit (CFU)/lungs at 28 days after treat

SUBMITTER: Chen C 

PROVIDER: S-EPMC5702905 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature