Title: Effects of ketoconazole on rat liver cytochrome P450
Abstract: Objective: To assess the effects of ketoconazole on rat cytochrome P450 and its main subtypes.Methods: SD male rats were ig administered with ketoconazole 140,280 or 420 μmol·kg-1 daily for 7 days.The rats were sacrificed under anesthesia to collect the liver tissues for measurement of total cytochrome P450 levels and activities of CYP450 subtypes CYP1A1,1A2,1B1,2B1/2,2E1 and 3A in the liver microsomes.Results: Ketoconazole significantly increased the liver/ body weight ratios and activities of CYP1A1 and 1B1 in a dose-dependent manner compared to the negative control group(P0.05,P0.01) and decreased total CYP450 levels and activities of CYP3A(P 0.01).Ketoconazole showed a reduction of CYP1A2 and 2B1/2 activities in the low dosing setting and an escalation of their activities in a high dosing setting(P0.05,P0.01).No impact of CYP2E1 activities by ketoconazole was found compared to the negative control group(P0.05).Conclusion: The monitoring of blood drug levels and the liver function may reduce the risks of cumulative toxicities and the loss of pharmacodynamic actions when ketoconazole is administered for a long run or adjunctively taken with other CYP450 inducers.
Publication Year: 2007
Publication Date: 2007-01-01
Language: en
Type: article
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Cited By Count: 1
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