title: Plasma pharmacokinetics and metabolism of the antitumour drug candidate 2'-benzoyloxycinnamaldehyde in rats.
abstract: The pharmacokinetics and metabolism of 2'-benzoyloxycinnamaldehyde (BCA) was characterized in male Sprague-Dawley rats as part of the preclinical evaluations for developing this compound as an antitumour agent. BCA was not detected in the plasma following either intravenous or oral dose, whereas its putative metabolites 2'-hydroxycinnamaldehyde (HCA) and o-coumaric acid were present at considerable levels. In separate pharmacokinetics studies, HCA exhibited a high systemic clearance and a large volume of distribution, whereas both pharmacokinetic parameters were much lower for o-coumaric acid. The terminal half-life of both metabolites was approximately 2 h. BCA was converted rapidly to HCA in rat serum, liver microsomes and cytosol in vitro; HCA was subsequently converted to o-coumaric acid in a quantitative manner only in the liver cytosol. In addition, the formation of o-coumaric acid was inhibited significantly by menadione, a specific inhibitor for aldehyde oxidase. Taken collectively, the results suggest that the rapid systemic clearance of HCA is likely due mainly to hepatic clearance occurring from aldehyde oxidase-catalysed biotransformation to o- coumaric acid. In conclusion, the present work demonstrates that the anticancer drug candidate BCA is highly likely to work as its active metabolite HCA in the body.
authors.affiliation: Bio-Evaluation Center, KRIBB, Chungbuk, Republic of Korea.
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.forename: Kangjeon
authors.initials: K
authors.lastname: Kim
authors.forename: Jekyung
authors.initials: J
authors.lastname: Ryu
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Kye Sook
authors.initials: KS
authors.lastname: Lee
authors.forename: Mu-Gil
authors.initials: MG
authors.lastname: Kwon
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001565:Benzoates / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: C484327:2'-benzoyloxycinnamaldehyde; D000970:Antineoplastic Agents; D001565:Benzoates; D000171:Acrolein