Optimal pharmacokinetic sampling
Clinical trials should incorporate pharmacokinetic sampling to confirm tizoxanide plasma exposures, and further validate the predictions from the PBPK model. Optimal sparse pharmacokinetic timepoint selection (assuming four blood samples per patient, and 40 patients in the study) was made on the basis of the prior fed pharmacokinetic data of Stockis et al. [29, 40]. Tizoxanide plasma pharmacokinetic data in fed patients from Stockis et al. was fitted with an empirical one‑compartment disposition model, with first-order absorption and absorption transit compartment, and the parameters from this fitting were used (with nominal %CV interindividual variability in the pharmacokinetic parameters of 30%) in the optimal design software PopDes (University of Manchester Version 4.0) to generate the suggested optimal sampling timepoints [45, 46].