The In Vitro Hepatic Metabolism of Quinine in Mice, Rats and Dogs: Comparison with Human Liver Microsomes
作者： Takashi Ishizaki , Xue-Jun Zhao
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摘要: The major metabolic pathway of quinine in the human has been shown to be 3-hydroxylation mediated mainly by cytochrome P450 (CYP) 3A4. In this extended vitro study, was further investigated using microsomes from mouse, rat, dog and livers compared among them terms enzyme-kinetic parameters quinine-drug interaction screenings. all species, 3-hydroxyquinine principal metabolite quinine. There intra- interspecies variability kinetic parameters, dogs exhibited a closer resemblance humans mean data. Ketoconazole troleandomycin inhibited species. Both alpha-naphthoflavone diazepam showed an difference 3-hydroxylation: trend toward activation human, significant inhibition mouse liver microsomes. Antisera raised against rat CYP3A2 strongly about 96, 84 92% with microsomes, respectively, but neither anti-rat 2C11 2E1 antisera did so Primaquine, doxycycline tetracycline substantially formation proguanil had no such effect any Chloroquine not correlation (r = 0.986, P < .001) between CYP3A contents rates eight microsomal samples. It is concluded that main CYP3A/Cyp3a isoform involved respective (rat, human/mouse) species tested. possibly may qualitatively quantitatively suitable animal models for exploring 3-hydroxylase activity screening interactions vitro, at certain inconsistency
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