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

Drug Metab Pharmacokinet. 2015 Apr;30(2):168-73. doi: 10.1016/j.dmpk.2014.12.003. Epub 2014 Dec 9.


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 (Tmax = 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 (Kp) far greater than unity for all tissues. In particular, its distribution to lipid was notably high (Kp = 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.

Keywords: Bioavailability; Elimination; Obesity; Pharmacokinetics; Tissue distribution; α-cedrene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / pharmacokinetics*
  • Anti-Obesity Agents / urine
  • Biological Availability
  • Biotransformation
  • Feces / chemistry
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Gastrointestinal Absorption
  • Hydroxylation
  • Injections, Intravenous
  • Intestinal Elimination
  • Male
  • Polycyclic Sesquiterpenes
  • Rats, Sprague-Dawley
  • Renal Elimination
  • Reproducibility of Results
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / pharmacokinetics*
  • Sesquiterpenes / urine
  • Tissue Distribution


  • Anti-Obesity Agents
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • cedrene