Fig. 3.

The (A) P450 kinetic model was developed to account for individual P450 pathways using previous data that identified the enzymes and their respective fm values that are relevant to THC and 11-OH-THC disposition in pooled HLMs (Patilea-Vrana et al., 2019). (B) The UGT kinetic model was not split up to account for individual UGT pathways due to lack of selective UGT inhibitors (Patilea-Vrana et al., 2019). The P450 and UGT kinetic models were fitted to the concentration–time profiles of THC, 11-OH-THC, and COOH-THC after incubation with either THC (green arrow) or 11-OH-THC (blue arrow) in the absence or presence of sulfaphenazole (SLF, CYP2C9 inhibitor) and itraconazole (ITZ, CYP3A inhibitor). Kinetic models were fit to data from three to four independent experiments. Kinetic parameters from Table 2 were used as initial estimates. Description of the governing ordinary differential equations can be found in the Supplemental Material.