Inhibition of cytochrome P450 2A participating in coumarin 7-hydroxylation in pig liver microsomes.

Z-Y Liu, M-H Dai, Y-F Tao, D-M Chen, Z-H Yuan

National Reference Laboratory of Veterinary Drug Residues (HZAU)/MAO Key Laboratory of Food Safety Evaluation, Huazhong Agricultural University, Wuhan, Hubei, China.

Journal of veterinary pharmacology and therapeutics 2011 Oct

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Five commonly used human cytochrome P450 (CYP) inhibitors were examined for their effects on coumarin 7-hydroxylase (CYP2A) activity in pig liver microsomes. The K(m) and V(max) values for coumarin 7-hydroxylation in pig liver microsomes were estimated to be 1 μm and 0.26 nmol·mg/min, respectively. The following human CYP inhibitors caused little or no inhibition of CYP2A as defined by a K(i) > 200 μm: quinidine (CYP2D6), troleandomycin (CYP3A4), and sulfaphenazole (CYP2C9). The other two human CYP inhibitors were classified as strong inhibitors of CYP2A: 8-methoxypsoralen (CYP2A6) and α-naphthoflavone (CYP1A1/2). In the absence of a preincubation period, 8-MOP inhibited the 7-hydroxylation of coumarin with a K(i) value of 1.1 μm, which decreased to 0.1 μm when 8-MOP was preincubated with pig liver microsomes for 3 min. α-Naphthoflavone inhibited the 7-hydroxylation of coumarin with a K(i) value of 32 μm, which did not increase ability to inhibitor CYP2A when α-naphthoflavone was preincubated with pig liver microsomes for 3 min. These results of this study suggest that 8-MOP is a potent, mechanism-based inhibitor of pig CYP2A activity in pig liver microsomes. © 2011 Blackwell Publishing Ltd.

Citation

Z-Y Liu, M-H Dai, Y-F Tao, D-M Chen, Z-H Yuan. Inhibition of cytochrome P450 2A participating in coumarin 7-hydroxylation in pig liver microsomes. Journal of veterinary pharmacology and therapeutics. 2011 Oct;34(5):424-9