In vivo absorption and disposition of α-cedrene, a sesquiterpene constituent of cedarwood oil, in female and male rats. Issue 2 (April 2015)

• Record Type: Journal Article
• Authors: Kim, Tae Hwan; Yoo, Sun Dong; Lee, Hye Suk; Lee, Kyoung Mee; Seok, Su Hyun; Kim, Min Gi; Jung, Byung Hwa; Kim, Min Gyu; Shin, Beom Soo
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 30:Issue 2(2015)
• Page Start: 168
• Page End: 173
• Publication Date: 2015-04
• Subjects: α-cedrene -- Bioavailability -- Pharmacokinetics -- Obesity -- Tissue distribution -- Elimination; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2014.12.003
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: This study aimed to evaluate the potential of α-cedrene as a new anti-obesity drug by characterizing absorption, metabolism and pharmacokinetics in rats. α-Cedrene was administered intravenously (10 and 20 mg/kg) and orally (50 and 100 mg/kg) to female and male Sprague–Dawley rats. Blood, tissues, urine, and feces were collected at predetermined times. α-Cedrene concentrations were determined by a validated gas chromatography–tandem mass spectrometry (GC–MS/MS). A gas chromatography–mass selective detection (GC–MSD) method was used to identify the major metabolite. After i.v. injection, α-cedrene exhibited a rapid clearance (98.4–120.3 ml/min/kg), a large distribution volume (35.9–56.5 l/kg), and a relatively long half-life (4.0–6.4 h). Upon oral administration, it was slowly absorbed ( T max = 4.4 h) with bioavailability of 48.7–84.8%. No gender differences were found in its pharmacokinetics. Upon oral administration, α-cedrene was highly distributed to tissues, with the tissue-to-plasma partition coefficients ( K p ) far greater than unity for all tissues. In particular, its distribution to lipid was notably high ( K p = 132.0) compared to other tissues. A mono-hydroxylated metabolite was identified as a preliminary metabolite in rat plasma. These results suggest that α-cedrene has the favorable pharmacokinetic characteristics to be further tested as an anti-obesity drug in clinical studies. Graphical abstract: