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].