title: In vivo absorption and disposition of α-cedrene, a sesquiterpene constituent of cedarwood oil, in female and male rats.
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 (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.
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors: Tae Hwan
authors: TH
authors: Kim
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors: Sun Dong
authors: SD
authors: Yoo
authors: College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do, Republic of Korea.
authors: Hye Suk
authors: HS
authors: Lee
authors: Kwang Dong Pharmaceutical Co., Ltd., Seoul, Republic of Korea.
authors: Kyoung Mee
authors: KM
authors: Lee
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors: Su Hyun
authors: SH
authors: Seok
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors: Min Gi
authors: MG
authors: Kim
authors: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, Republic of Korea; University of Science and Technology, Daejeon, Republic of Korea.
authors: Byung Hwa
authors: BH
authors: Jung
authors: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Republic of Korea.
authors: Min Gyu
authors: MG
authors: Kim
authors: College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk, Republic of Korea. Electronic address: bsshin@cu.ac.kr.
authors: Beom Soo
authors: BS
authors: Shin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D001711:Biotransformation; D005243:Feces / Q000737:chemistry; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D065569:Gastrointestinal Absorption; D006900:Hydroxylation; D007275:Injections, Intravenous; D066237:Intestinal Elimination; D008297:Male; D000081223:Polycyclic Sesquiterpenes; D017207:Rats, Sprague-Dawley; D065667:Renal Elimination; D015203:Reproducibility of Results; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
chemical_list: D019440:Anti-Obesity Agents; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C000393:cedrene
keywords: Bioavailability; Elimination; Obesity; Pharmacokinetics; Tissue distribution; α-cedrene