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. 2020 Jul 15;117(30):18059–18067. doi: 10.1073/pnas.2002704117

Fig. 5.

Fig. 5.

Phase I metabolism and brain/plasma distribution of compound JH112. (A) Exposure of suvorexant and JH112 to rat liver microsomes over 60 min. Rotigotine and imipramine serve as positive controls for extensive phase I metabolism. Data represent mean ± SEM of n = 3 independent experiments. (B) Quantitative analysis of metabolite pool composition after 60 min by HPLC-MS reveals predominantly hydroxylated metabolites (M1 to M7). Total amount of JH112 and metabolite pool after 60 min is slightly lower than 100%, reflecting cumulative error in liquid chromatography–mass spectrometry analysis. (C) Pharmacokinetic studies of JH112 in female CD-1 mice (n = 3 animals for each time point) show central nervous system penetration of the compound, with a peak level of 122 ng of JH112 per gram of brain tissue after 30 min, with a maximum plasma concentration of 479 ng/mL after 10 min. All data are mean ± SEM.