Cytochrome P450-mediated hepatic metabolism of new fluorescent substrates in cats and dogs.
作者： C. D. Van BEUSEKOM , L. SCHIPPER , J. FINK-GREMMELS
DOI: 10.1111/J.1365-2885.2010.01199.X
关键词: Cytochrome P-450 Enzyme Inhibitors 、 Internal medicine 、 Drug metabolism 、 Cytochrome P450 、 Biology 、 Microsome 、 Endocrinology 、 Furafylline 、 CYP3A 、 Sulfaphenazole 、 CATS 、 Pharmacology
摘要: This study aimed to investigate the biotransformation of cat liver microsomes in comparison dogs and humans using a high throughput method with fluorescent substrates classical inhibitors specific for certain isozymes human cytochrome P450 (CYP) enzyme family. The metabolic activities associated CYP1A, CYP2B, CYP2C, CYP2D, CYP2E CYP3A were measured. Cat metabolized all selected assessment activity. CYP2B higher than other measured CYPs. Substrate selectivity could be demonstrated by inhibition studies α-naphthoflavone (CYP1A), tranylcypromine/quercetine (CYP2C), quinidine (CYP2D), diethyldithiocarbamic acid (CYP2E) ketoconazole (CYP3A) respectively. Other prototypical used characterization CYP such as furafylline tranylcypromine (CYP2B) sulfaphenazole (CYP2C) did not show significant effects dog microsomes. Moreover, IC50-values CYPs differed from underlining interspecies differences. Gender differences observed oxidation 7-ethoxy-4-trifluoromethylcoumarin 3-[2-(N, N-diethyl-N-methylamino)ethyl]-7-methoxy-4-methylcoumarin which significantly male cats females. Conversely, dibenzylfluorescein 7-methoxy-4-trifluoromethylcoumarin showed females cats. Overall CYP-activities lower those or humans, except CYP2B. presented difference between feline canine are useful establish dose corrections patients intensively drugs licensed humans.
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Michael H. Court, David J. Greenblatt, Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes. Biochemical Pharmacology. ,vol. 53, pp. 1041- 1047 ,(1997) , 10.1016/S0006-2952(97)00072-5
Jeroen T.M. Buters, Claus D. Schiller, Ruby C. Chou, A highly sensitive tool for the assay of cytochrome P450 enzyme activity in rat, dog and man. Direct fluorescence monitoring of the deethylation of 7-ethoxy-4-trifluoromethylcoumarin. Biochemical Pharmacology. ,vol. 46, pp. 1577- 1584 ,(1993) , 10.1016/0006-2952(93)90326-R
Victoria A. Eagling, John F. Tjia, David J. Back, Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes British Journal of Clinical Pharmacology. ,vol. 45, pp. 107- 114 ,(1998) , 10.1046/J.1365-2125.1998.00679.X
D. J. Newton, R. W. Wang, A. Y. H. Lu, Cytochrome P450 inhibitors. Evaluation of specificities in the in vitrometabolism of therapeutic agents by human liver microsomes. Drug Metabolism and Disposition. ,vol. 23, pp. 154- 158 ,(1995)
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
S N Binkley, S A Wrighton, L A Shipley, J E Sharer, M R Vandenbranden, Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. Drug Metabolism and Disposition. ,vol. 23, pp. 1231- 1241 ,(1995)
Takashi Ishizaki, Xue-Jun Zhao, The In Vitro Hepatic Metabolism of Quinine in Mice, Rats and Dogs: Comparison with Human Liver Microsomes Journal of Pharmacology and Experimental Therapeutics. ,vol. 283, pp. 1168- 1176 ,(1997)
Yoichi Naritomi, Yuriko Teramura, Shigeyuki Terashita, Akira Kagayama, Utility of Microtiter Plate Assays for Human Cytochrome P450 Inhibition Studies in Drug Discovery: Application of Simple Method for Detecting Quasi-irreversible and Irreversible Inhibitors Drug Metabolism and Pharmacokinetics. ,vol. 19, pp. 55- 61 ,(2004) , 10.2133/DMPK.19.55
K. BrØsen, B.B. Rasmussen, U. Jeppesen, T.L. Nielsen, Drug interactions on the level of cytochrome P450: Pharmacokinetic, pharmacogenetic and clinical aspects Biological Psychiatry. ,vol. 42, pp. 127- ,(1997) , 10.1016/S0006-3223(97)87425-2
Shu-Feng Zhou, Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clinical Pharmacokinectics. ,vol. 48, pp. 689- 723 ,(2009) , 10.2165/11318030-000000000-00000