Pharmacokinetics

Favipiravir exposure remained above estimated effective concentrations throughout treatment. Pharmacokinetic sampling 4 to 8 weeks after treatment initiation is preferred because early disease-response variability and treatment adjustments have usually stabilised by that point. Pharmacokinetic data will be analyzed with efficacy endpoints to explore exposure-response relationships. Favipiravir nonlinearity could not be excluded because the trial had a small sample size. Clofazimine and bedaquiline are exceptions to reaching steady-state by the preferred sampling window due to their long half-lives and accumulation patterns. Favipiravir pharmacokinetics were best described by a one-compartment model with oral absorption, absorption lag time, and linear elimination. Favipiravir exposure was higher on day 1 than at steady state because the loading dose rapidly attained therapeutic concentrations. Higher body weight correlated with higher favipiravir clearance. Drug concentrations for isoniazid, clofazimine, bedaquiline and fluoroquinolones will be quantified by liquid chromatography mass spectrometry at the University of Cape Town. The Namibian study uses both intensive and sparse ph…