Mimicking in-vivo exposures to drug combinations in-vitro: anti-tuberculosis drugs in lung lesions and the hollow fiber model of infection.

ABSTRACT: Here, we evaluate protocol requirements to mimic therapeutically relevant drug concentrations at the site of infection (i.e. lung lesion) in an in-vitro hollow fibre model of infection using pulmonary tuberculosis as a paradigm. Steady-state pharmacokinetic profiles in plasma, lung tissue and lung lesion homogenate were simulated for isoniazid, rifampicin and pyrazinamide and moxifloxacin. An R-shiny User Interface was developed to support conversion of in-vivo pharmacokinetic C_MAX, T_MAX and T_1/2 estimates into pump settings. A monotherapy protocol mimicking isoniazid in lung lesion homogenate (isoniazid C_MAX = 1,200 ng/ml, T_MAX = 2.2 hr and T_1/2 = 4.7 hr), and two combination therapy protocols including drugs with similar (

SUBMITTER: Kloprogge F 

PROVIDER: S-EPMC6744479 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature