RT Journal Article
SR Electronic
T1 Presence and Activity of Cytochrome P450 Isoforms in Minipig Liver Microsomes
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 56
OP 59
VO 26
IS 1
A1 Pavel Anzenbacher
A1 Pavel Soucek
A1 Eva Anzenbacherová
A1 Ivan Gut
A1 Kamil Hruby
A1 Zbynek Svoboda
A1 Jaroslav Kvetina
YR 1998
UL http://dmd.aspetjournals.org/content/26/1/56.abstract
AB 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 6β-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-PentoxyresorufinO-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. The American Society for Pharmacology and Experimental Therapeutics