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Pharmacokinetics of 5-fluorouracil in mutant Nagase analbuminemic rats: faster metabolism of 5-fluorouracil via CYP1A

✍ Scribed by Young H. Choi; Soo K. Bae; Sun O. Kim; Myung G. Lee

Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
133 KB
Volume
28
Category
Article
ISSN
0142-2782

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✦ Synopsis

Abstract

It has been reported that plasma albumin concentrations were significantly lower in cancer patients than those in the healthy volunteers, and the expression and mRNA level of hepatic microsomal cytochrome P450 (CYP) 1A2 increased in mutant Nagase analbuminemic rats (NARs). After intravenous administration of 5‐fluorouracil at a dose of 30 mg/kg to NARs, the time‐averaged nonrenal clearance (Cl~nr~) of the drug was significantly faster than the controls (51.3 versus 28.8 ml/min/kg), possibly due to an increase in the expression and mRNA level of CYP1A2 in NARs. In order to determine whether 5‐fluorouracil is metabolized via CYP1A2 in male Sprague–Dawley rats, the rats were pretreated with 3‐methylcholanthrene (a main inducer of CYP1A1/2 in rats). The Cl~nr~ of 5‐fluorouracil was significantly faster (34.3 versus 27.3 ml/min/kg) in rats pretreated with 3‐methylcholanthrene. The aforementioned data indicate that CYP1A is involved in the metabolism of 5‐fluorouracil in rats. Copyright © 2007 John Wiley & Sons, Ltd.

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