Elsevier

Biochemical Pharmacology

Volume 42, Issue 11, 6 November 1991, Pages 2241-2244
Biochemical Pharmacology

Short communication
Impairment of bunitrolol 4-hydroxylase activity in liver microsomes of Dark Agouti rats

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Cited by (31)

  • Pharmacokinetics and metabolism of metoprolol and propranolol in the female DA and female Wistar rat: The female DA rat is not always an animal model for poor metabolizers of CYP2D6

    2005, Journal of Pharmaceutical Sciences
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    However, because there are no definite criteria for a continue/discontinue decision in terms of genetic polymorphisms, alternative investigations are required to facilitate the prioritization of several development candidates and the selection of the compound to be developed. It has been reported that DA rats exhibit quite low mRNA levels of CYP2D2,5 and that liver microsomes from DA rats have low activities toward the biotransformation of some typical CYP2D6 substrates6–9 (debrisoquine, bunitrolol, alprenolol, and metoprolol), compared to other strains. Therefore, DA rats may be regarded as an animal model for poor metabolizers (PM).

  • Complementary DNA cloning and characterization of cytochrome P450 2D29 from Japanese monkey liver

    2002, Biochemical Pharmacology
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    An aliquot (10 μL) of the supernatant was subjected to HPLC under the conditions described below. BF 1″-hydroxylase activity was assayed by a similar HPLC method used previously for BTL 4-hydroxylase assay [30,31]. Briefly, a 500-μL incubation mixture in a brown glass conical tube (10 mL) with a stopper contained 0.3 to 0.5 mg microsomal protein, 5 mM G-6-P, 5 mM MgCl2, 0.1 mM EDTA, 0.5 mM NADPH, and 100 μM BF racemate in 100 mM potassium phosphate buffer (pH 7.4).

  • Species difference in enantioselectivity for the oxidation of propranolol by cytochrome P450 2D enzymes

    2000, Chemico-Biological Interactions
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    As an appropriate animal model to mimic humans in drug metabolism in vitro, subcellular fractions of various monkey organs or tissues have been extensively studied, and it is generally recognized that the monkey is not always similar to humans in drug oxidation [6–11]. We have been studying the characteristics of drug oxidation by CYP2D enzymes in various animal species such as mice [12], rats [13,14], monkeys [15] and humans [16–18] using adrenoceptor blocking agents (β-blockers) or calcium channel blockers as substrates. In the course of our studies, we found that 4-hydroxylation of bunitrolol (BTL), a β-blocker, is mainly mediated by CYP2D2 in rats [13,14] and by CYP2D6 in humans [19] especially at the clinically relevant low substrate concentrations.

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Current address: Department of Toxicology, Faculty of Veterinary Medicine, Hokkaido University, North 18, West 9, Sapporo, Japan.

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