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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples.

Cytochrome P450 (CYP) of the 3A family ( CYP3A) has been detected in minipig liver microsomes by immunochemical screening (Western blotting), revealing bands that co-migrate with human CYP3A4 and 3A5. The nifedipine oxidase activity and testosterone 6beta-hydroxylating activity (specific markers for CYP3A enzymes) of the human liver microsomal and minipig liver microsomal samples were comparable, as were the results of specific inhibition of this activity by triacetyloleandomycin. The presence of CYP1A, 2A, 2C, 2D, and 2E1 marker activities in minipig liver microsomes was found by testing with the respective specific substrates (7-ethoxyresorufin, coumarin, tolbutamide, bufuralol, and chlorzoxazone). 7-Pentoxyresorufin O-depentylase activity (indicative of CYP2B) was absent from minipig as well as human liver microsomal samples. The results indicate that minipigs might be, in many cases, the most suitable experimental animals to predict biotransformation pathways in humans, because the activity of the most important CYP isoform in humans ( CYP3A, metabolizing the majority of known drug substrates) is present in minipigs, with comparable levels and activities. Moreover, there is no need to induce CYP enzyme levels.[1]

References

  1. Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples. Anzenbacher, P., Soucek, P., Anzenbacherová, E., Gut, I., Hrubý, K., Svoboda, Z., Kvĕtina, J. Drug Metab. Dispos. (1998) [Pubmed]
 
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