Fig. 2.

Top: Six humanized TK-NOG mice were first dosed with clemizole (Clem) alone (25 mg/kg by mouth) and then with clemizole (25 mg/kg by mouth) and ritonavir (20 mg/kg by mouth). The amount of six different clemizole metabolites in plasma was measured at 30 minutes after administration. The plasma concentrations of the human-predominant M1 and M6 metabolites were significantly decreased by ritonavir coadministration, as were the concentrations of M2 and M12, whereas those of M14 and M15 were unchanged. Bottom: Five humanized TK-NOG mice were first given debrisoquine (Deb) alone (10 mg/kg by mouth) and then debrisoquine (10 mg/kg by mouth) and ritonavir (20 mg/kg by mouth). The amount of its main metabolite, 4-OH-debrisoquine, was measured in plasma 2 hours after administration. The relative amount of 4-OH debrisoquine was not significantly changed by ritonavir coadministration.