In vivo absorption and disposition of α-cedrene, a sesquiterpene constituent of cedarwood oil, in female and male rats

This study aimed to evaluate the potential of alpha-cedrene as a new anti-obesity drug by characterizing absorption, metabolism and pharmacokinetics in rats. alpha-Cedrene was administered intravenously (10 and 20 mg/kg) and orally (50 and 100 mg/kg) to female and male SpragueeDawley rats. Blood, tissues, urine, and feces were collected at predetermined times. alpha-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, alpha-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, alpha-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 alpha-cedrene has the favorable pharma-cokinetic characteristics to be further tested as an anti-obesity drug in clinical studies. Copyright (C) 2014, The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.