Characterization Of Cytochrome P450 Isozymes In Bama Miniature Pigs And Guizhou Miniature Pigs: Comparison With Human Analogs

Suitable animal models can mirror the metabolic attributes of human. Thus, the animal species whose metabolic properties similar to human should be chosen to develop data to further aid the estimation of metabolic potential in human. Therefore, the metabolic potential comparisons of experimental animals with human will help the researchers to choose an appropriate animal-based model both in drug development and clinical therapy.Chinese Bama miniature pigs and Guizhou miniature pigs has been used for comparative medicine research in China for a long time, because of its anatomical and physiological similarities with humans in the cardiovascular, gastrointestinal, renal systems and the skin. With the increasing use of Chinese Bama miniature pigs and Guizhou miniature pigs in pre-clinical drug evaluation, it is necessary to identify their hepatic drug metabolizing characteristics. However, there is still no knowledge about the Chinese Bama miniature pigs and Guizhou miniature pigs hepatic drug metabolizing system.In the present study, substrates and selective inhibitors of human cytochrome P450 isozymes were used as probes to study the metabolism in Chinese Bama miniature pigs and Guizhou miniature pigs liver microsomes. Comparable levels of nifedipine oxidation (NOD), testosterone 6β-hydroxylation (6β-OHT) activities were observed in liver microsomes from Chinese Bama miniature pigs, Guizhou miniature pigs and human. Phenacetin O-deethylation (POD), coumarin 7-hydroxylation (CH) and chlorzoxazone 6-hydroxylation (CZH) activities of Chinese Bama miniature pigs and Guizhou miniature pigs liver microsomes were lower than those observed in human liver microsomes. Elevated dextromethorphan O-demethylation (DMOD) activity was observed in Chinese Bama miniature pigs and Guizhou miniature pigs liver microsomes. For the inhibition study, ketoconazole selectively inhibited miniature pigs NOD and 6β-OHT activities. Miniature pigs CH activity was inhibited in the presence of 8-methoxypsoralen and tranylcypromine. However, furafylline and quinidine didn't selectively inhibit the corresponding POD and...