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KMID : 0379520080240030195
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한국독성학회지
2008 Volume.24 No. 3 p.195 ~ p.199
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Effects of Oral Rutaecarpine on the Pharmacokinetics of Intravenous Chlorzoxazone in Rats
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Sudeep R. Bista
Kim Jung-Ae
Jahng Yurng-Dong
Jeong Tae-Cheon
Kim Dong-Hyeon
Kang Mi-Jeong
Seo Young-Min
Kim Ju-Hyun
Lee Sang-Kyu
Dinesh Thapa
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Abstract
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It has been reported that hepatic microsomal cytochrome P450 (CYP) 2E1 is responsible for the metabolism of chlorzoxazone (CZX) to 6-hydroxychlorzoxazone. The present study was undertaken to assess the possible interaction of rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, with CZX. Male Spraque-Dawley rats were administered with 80 mg/kg/day of oral rutaecarpine for three consecutive days. Twenty four hr after the pre-treatment with rutaecarpine, the rats were treated with 20 ㎎/㎏ of intravenous CZX. Rat hepatic microsomes isolated from rutaecarpine-treated rats showed greater (50% increase) activity of p-nitrophenol hydroxylase (a marker of CYP2E1) when compared with the control rats. Compared with control rats, the AUC of CZX was significantly smaller (84% decrease) possibly due to significantly faster CL (646% increase) in rats pretreated with rutaecarpine. This could be, at least partially, due to induction of CYP2E1 by rutaecarpine.
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KEYWORD
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Rutaecarpine, Chlorzoxazone, Interaction, Pharmacokinetics, CYP2E1, In vivo
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