title: Pharmacokinetic analysis of enterohepatic circulation of buprenorphine and its active metabolite, norbuprenorphine, in rats.
abstract: The pharmacokinetic characteristics of buprenorphine (BN) and its active metabolite, norbuprenorphine (NBN), was investigated using rats. The elimination half-life (t1/2), total body clearance (CLtot), and steady-state volume of distribution (Vdss) of BN (0.6 mg/kg iv dose) in the intact rat were 2.8 hr, 23.3 ml/min/kg, and 4.2 liters/kg, respectively, and those of NBN (0.6 mg/kg iv dose) were 0.9 hr, 35.0 ml/min/kg, and 2.0 liters/kg. Within 24 hr after administration of BN (0.6 mg/kg dose) to the bile-fistula rat, 74.1% of dose was excreted in the bile as BN glucuronide (BN-Glu) and 18.5% as NBN glucuronide (NBN-Glu), and in urine < 3.2% as BN-Glu. After administration of NBN to the bile-fistula rat, 85.1% and 9.1% of the dose were excreted as NGN-Glu in bile and urine, respectively. The existence of the enterohepatic circulation (EHC) of BN and NBN was confirmed by using paired rats: the donor and recipient rats. Within 24 hr after administration of BN (0.6 mg/kg dose) to the donor rat, 58.8% of the dose was reexcreted as NBN-Glu in bile of the recipient and 25.1% as BN-Glu. Based on the results of in vitro metabolism, it was suggested that this increase in the proportion of NBN-Glu in bile observed after one enterohepatic cycling of BN may be due to the first-pass metabolism in the liver. BN was detected in the plasma of the recipient rat after administration of BN, to the donor rat.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohtani
authors.forename: H
authors.initials: H
authors.lastname: Kotaki
authors.forename: K
authors.initials: K
authors.lastname: Uchino
authors.forename: Y
authors.initials: Y
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Iga
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002047:Buprenorphine; C043585:norbuprenorphine