2.6 Adult PBPK model validation against available clinical data
The oral regimens tested in adults included: 30 mg CAB single dosing and
30 mg CAB repeated dosing for CAB [34, 42]; 25 mg RPV and 150 mg RPV
repeated dosing [43-46]; and 400 mg RAL single and repeated dosing
[47, 48]. Similarly, the LAI regimens tested in adults included: 800
mg IM CAB followed by 200 mg IM CAB monthly, 800 mg IM CAB followed by
400 mg IM CAB monthly, and 800 mg IM CAB every 3 months; and 1200 mg IM
RPV followed by 600 mg IM RPV monthly and 1200 mg IM RPV followed by 900
mg IM RPV monthly [34].
PK parameters of each drug were simulated and compared with the
corresponding adult data from clinical studies available in literature
to validate the adult PBPK model. The doses, regimens and routes of drug
administration were modelled to mimic the clinical studies used to
validate the model. The model validation process was conducted in line
with the European Medicines Agency (EMA) guidelines for PBPK model
qualification [49]. Each model was considered validated when the
summary statistics (mean or median) of the simulated PK parameters such
as AUC, Cmin and Cmax were less than
two-fold of the reported clinical values and the absolute average fold
error (AAFE) was also less than two.