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Research ArticleArticle

Presence and Activity of Cytochrome P450 Isoforms in Minipig Liver Microsomes

Comparison with Human Liver Samples

Pavel Anzenbacher, Pavel Soucek, Eva Anzenbacherová, Ivan Gut, Kamil Hruby, Zbynek Svoboda and Jaroslav Kvetina
Drug Metabolism and Disposition January 1998, 26 (1) 56-59;
Pavel Anzenbacher
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Pavel Soucek
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Eva Anzenbacherová
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Ivan Gut
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Kamil Hruby
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Zbynek Svoboda
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Jaroslav Kvetina
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Comparison with Human Liver Samples

Abstract

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.

Footnotes

  • Send reprint requests to: Dr. Pavel Anzenbacher, Institute of Experimental Biopharmaceutics, Heyrovský str. 1207, 500 02 Hradec Králové, Czech Republic.

  • This project was supported by the Grant Agency of the Czech Republic (grant 203/96/0177) and by the Grant Agency of the Ministry of Health (grants IGA 3505–3 and 2763–4).

  • Abbreviations used are::
    CYP
    cytochrome P450
    TAO
    triacetyloleandomycin
    • Received April 9, 1997.
    • Accepted September 15, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition
Vol. 26, Issue 1
1 Jan 1998
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Research ArticleArticle

Presence and Activity of Cytochrome P450 Isoforms in Minipig Liver Microsomes

Pavel Anzenbacher, Pavel Soucek, Eva Anzenbacherová, Ivan Gut, Kamil Hruby, Zbynek Svoboda and Jaroslav Kvetina
Drug Metabolism and Disposition January 1, 1998, 26 (1) 56-59;

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Research ArticleArticle

Presence and Activity of Cytochrome P450 Isoforms in Minipig Liver Microsomes

Pavel Anzenbacher, Pavel Soucek, Eva Anzenbacherová, Ivan Gut, Kamil Hruby, Zbynek Svoboda and Jaroslav Kvetina
Drug Metabolism and Disposition January 1, 1998, 26 (1) 56-59;
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