For the development of new drugs, evaluation of drug-drug interactions with already known compounds, as well as for better understanding of metabolism pathways of various toxicants and pollutants, we studied the drug metabolism mediated by cytochromes P450. The experimental approach is based on animal drug-metabolising systems. From the ethical as well as rational reasons, the selection of an appropriate system is crucial. Here, it is necessary to decide on the basis of expected CYP system involved. For CYP1A-mediated pathways, all the commonly used experimental models are appropriate except probably the dog. On the contrary, the dog seems to be suitable for modelling of processes depending on the CYP2D. With CYP2C, which is possibly the most large and complicated subfamily, the systems based on monkey (Maccacus rhesus) may be a good representative. The CYP3A seems to be well modelled by pig or minipig CYP3A29. Detailed studies on activities with individual isolated CYP forms are needed to understand in full all aspects of inter-species differences and variations.

Department of Medical Chemistry and Biochemistry Faculty of Medicine Palacky University at Olomouc Hnevotínská 3 775 15 Olomouc Czech Republic

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Ortiz de Montellano P.R., (ed.), Cytochromes P450, Plenum Press, New York 1995.

Anzenbacher P., Anzenbacherová E., Cytochromes P450 and metabolism of xeno‐biotics, Cell. Mol. Life Sci., 58: 737, 2001. PubMed PMC

McLean M.A., Maves S.A., Weiss K.E., Krepich S., Sligar S.G., Characterization of a cytochrome P450 from the acidothermophilic archaea Sulfolobus solfataricus, Biochem. Biophys. Res. Commun., 252: 166, 1998. PubMed

Nelson D.R., Cytochrome P450 and the individuality of species, Arch. Biochem. Biophys., 369: 1–10, 1999. PubMed

For P450 pages on Internet, start e.g. with the http://mhc.com/cytochromes/links.HTML or with http://drnelson.utmem.edu/cytochromeP450.html.

Krishna D., Klotz U., Exrtahepatic metabolism of drugs in humans, Clin. Pharmacokinet., 26: 144, 1994. PubMed

Mandelbaum A., Pertyborn F., Martin/Facklam M., Wiesel M., Unexplained decrease of cyclosporin trough levels in a compliant renal transplant patient, Nephrol. Dialysis Transplantation, 15: 1473, 2000. PubMed

Mai I., Krüger H., Budde K., Johne A., Brockmöller J., Neumayer H.H., Roots I., Hazardous pharmacokinetic interaction of Saint John's wort (Hypericum perforatum) with the immunosuppressant cyclosporin, Int. J. Clin. Pharmacol. Therapeutics, 38: 500, 2000. PubMed

Thummel K.E., Wilkinson G.R., In vitro and in vivo drug interactions involving human CYP3A, Annual Rev. Pharmacol. Toxicol., 38: 389, 1998. PubMed

Mullins M.E., Horowitz B.Z., Linden D.H., Smith G.W., Norton R.L., Stump J., Life‐threatening interaction of mibefradil and beta‐blockers with dihydropyridine calcium channel blockers, JAMA, 280: 157, 1998. PubMed

Dresser G.K., Spencer D.J., Bailey D.G., Pharmacokinetic‐pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition, Clin. Pharmacokinet., 38: 41, 2000. PubMed

Bertz R.J., Granneman G.R., Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions, Clin. Pharmacokinet. 32: 210, 1997. PubMed

Guengerich F.P., Human cytochrome P450 enzymes. In: Ref. 1, pp. 473–535.

Cooper D.J., Gollackner B., Sachs D.H., Will the pig solve the transplantation backlog?, Annu. Rev. Med., 53: 133, 2002. PubMed

Guengerich F.P., Comparisons on catalytic selectivity of cytochrome P450 subfamily enzymes from different species, Chem.-Biol. Interact., 106: 161, 1997. PubMed

Smith D.A., Species differences in metabolism and pharmacokinetics: Are we close to an understanding?, Drug Metabol. Revs., 23: 355, 1991. PubMed

Aleynik M.K., Lieber C.S., Dilinoleylphosphatidylcholine decreases ethanol‐induced cytochrome P450 2E1, Biochem. Biophys. Res. Commun., 288: 1047, 2001. PubMed

Lu C., Li A.P., Species comparison in cytochrome P450 induction: Effects of dexamethasone, omeprazole, and rifampine on P450 isoforms 1A and 3A in primary cultured hepatocytes form man, Sprague‐Dawley rat, minipig, and Beagle dog, Chem.-Biol. Interact. 134: 271, 2001. PubMed

Nedelcheva V., Gut I., P450 in the rat and man: Methods of investigation, substrate specifities and relevance to cancer, Xenobiotica, 24: 1151, 1994. PubMed

Strobl G.R., von Kruedener, S. , Stockigt J., Guengerich F.P., Wolff T., Development of a pharmacophore for inhibition of human liver cytochrome P450 2D6: Molecular modelling and inhibition studies, J. Med. Chem., 36: 1136, 1993. PubMed

Kobayashi K., Urashima K., Shimada T., Chiba K., Substrate specificity for rat cytochrome P450 (CYP) isoforms: Screening with cDNA‐expressed system of the rat, Biochem. Pharmacol., 63: 889, 2002. PubMed

Gonzalez F.J., Matsunaga Y., Nagata K., Meyer U.A., Nebert D.W., Pastewka J., Kozak C.A., Gillette J., Gelboin H.W., Hardwick J.P., Debrisoquine 4‐hydroxylase: Characterization of a new P450 gene subfamily., DNA, 6:149, 1987. PubMed

Quattrochi L.C., Tukey R.H., The human CYP1A2 gene and induction by 3‐methylcholanthrene, J.Biol.Chem., 269: 6949, 1994. PubMed

Haugen D.A., Coon M.J., Properties of electrophoretically homogenous phenobarbitalinducible and beta naphthoflavone‐inducible forms of liver microsomal cytochrome P‐450, J. Biol. Chem., 251: 7929, 1976. PubMed

Ding X., Pernecky S.J., Coon M.J., Purification and characterization of cytochrome P450 2E2 from hepatic microsomes of neonatal rabbits, Arch. Biochem. Bioiphys., 291: 270, 1991. PubMed

Schwartz P.S., Waxman D.J., Cyclophosphamide induces caspase 9‐dependent apoptosis in 9L tumor cells, Mol. Pharmacol., 60: 1268, 2001. PubMed

Waxman D.J., Attisano C., Guengerich F.P., Lapenson D.P., Cytochrome P450 steroid hormone metabolism catalyzed by human liver microsomes, Arch. Biochem. Biophys., 263: 424, 1988. PubMed

Yamamoto Y., Ishizuka M., Takada A., Fujita S., Cloning, tissue distribution, and functional expression of two novel rabbit cytochrome P450 isozymes, CYP2D23 and CYP2D24, J. Biochem. (Tokyo), 124: 503, 1998. PubMed

Bogaards J.J.P., Bertrand M., Jackson P., Oudshoorn M.J., Weaver R.J., van Bladeren P.J., Walther B., Determining the best animal model for human cytochrome P450 activities: Comparison of mouse, rat, rabbit, dog, micropig, monkey and man, Xenobiotica, 30: 1131, 2000. PubMed

Jayyosi Z., Muc M., Erick J., Thomas P.E., Kelley M., Catalytic and immunochemical characterization of cytochrome P450 isozyme induction in dog liver, Fundam. Appl. Toxicol., 31: 95, 1996. PubMed

Roussel F., Duignan D.B., Lawton M.P., Obach R.S., Strick C.S., Tweedie D.J., Expression and characterization of canine cytochrome P450 2D15, Arch. Biochem. Biophys., 357: 27, 1998. PubMed

Chauret N., Gauthier A., Martin J., Nicoll‐Griffith D.A., In vitro comparison of cytochrome P450‐mediated metabolic activities in human, dog, cat, and horse, Drug Metab. Disposition, 25: 1130, 1997. PubMed

Sharer J.E., Shipley L.A., Vandenbranden M.R., Binkley S.N., Wrighton S.A., Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey, Drug Metab. Disposition, 23: 1231, 1995. PubMed

Edwards R.J., Murray S., Schulz T., Neubert D., Gant T. W., Thorgeirsson S.S., Boobis A.R., Davis D.S., Contribution of CYP1A1 and CYP1A2 on the activation of heterocyclic amines in monkeys and human, Carcinogenesis, 15: 829, 1994. PubMed

Komori M., Kikuchi O., Sakuma T., Funaki J., Kitada M., Kamataki T., Molecular cloning of monkey liver cytochromes P‐450 cDNAs: Similarity of the primary sequences to human cytochromes P‐450, Biochim. Biophys. Acta, 1171: 141, 1992. PubMed

Anzenbacher P., Souèek P., Anzenbacherová E., Gut I., Hrubý K., Svoboda Z., Kvìtina J., Presence and activity of cytochrome P450 isoforms in minipig liver microsomes, Drug Metab. Disposition, 26: 56, 1998. PubMed

Skaanild M.T., Friis C., Characterization of the P450 system in Goettingen minipigs, Pharmacol. Toxicol., 80 (Suppl. 2): 28, 1997. PubMed

Monshouwer M., van't Klooster G.A.E., Nijmeijer S.M., Witkamp R.F., van Miert A.S.J.P.A.M., Characterization of cytochrome P450 isoenzymes in primary cultures of pig hepatocytes, Toxicol. In Vitro, 12: 715, 1998. PubMed

Myers M.J., Farrell D.E., Howard K.D., Kawalek J.C., Identification of multiple constitutive and inducible hepatic cytochrome P450 enzymes in market weight swine, Drug Metab. Disposition, 29: 908, 2001. PubMed

Hosseinpour F., Wikvall K., Porcine microsomal vitamin D3 25‐hydroxylase (CYP2D25), J. Biol. Chem., 275: 34650, 2000. PubMed

Clement B., Lomb R., Möller W., Isolation and characterization of the protein components of the liver microsomal O2‐insensitive NADH‐benzamidoxime reductase, J. Biol. Chem., 272: 19615, 1997. PubMed

Nissen P.H., Wintero A.K., Fredholm M., Mapping of porcine genes belonging to two different cytochrome P450 subfamilies, Animal Genetics, 29: 7, 1998. PubMed

Souèek P., Zuber R., Anzenbacherová E., Anzenbacher P., Guengerich F.P., Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs, BMC Pharmacology, 1: 11, 2001. PubMed PMC

Olsen A., Hansen K.T., Friis C., Pig hepatocytes as an in vitro model to study the regulation of human CYP3A4: prediction of drug‐drug interactions with 17β‐ethynylestradiol, Chem.-Biol. Interact., 107: 93, 1997. PubMed

Anzenbacher P., Anzenbacherová E., Zuber R., Souèek P., Guengerich F.P., Pig and minipig cytochromes P450, Drug Metab. Disposition, 30: 100, 2002. PubMed

Takemori S., Kominami S., The role of cytochromes P450 in adrenal steroidogenesis, Trends Biochem. Sci., 9: 393, 1984.

Differences in mRNA Expression of Selected Cytochrome P450, Transporters and Nuclear Receptors Among Various Rat Models of Metabolic Syndrome

Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population

Effect of methamphetamine on the pharmacokinetics of dextromethorphan and midazolam in rats