title: Metabolism of bucolome in rats. Stability and biliary excretion of bucolome N-glucuronide.
abstract: Bucolome (BCP) is a non-steroidal anti-inflammatory drug, which is used in the treatment of chronic articular rheumatism. Bucolome N-glucuronide (BCP-NG), a metabolite of BCP, is the first unique N-glucuronide of barbituric acid derivatives. First, the stability of BCP-NG in various pH aqueous solutions was studied. BCP-NG was quite unstable under neutral and acidic conditions, and is easily hydrolyzed to BCP. Based on these characteristics of BCP-NG, a simple, rapid and highly sensitive method for the simultaneous determination of BCP and BCP-NG with phenylbutazone (I.S.) in biological fluids was developed using high-performance liquid chromatography (HPLC). A reversed-phase ODS column was used for the separation of BCP, BCP-NG and I.S. A pharmacokinetic study for BCP and BCP-NG was carried out in male Wistar/ST rats following i.v. administration of BCP at a dose of 10 mg/kg body weight. The slow plasma elimination of BCP with time was shown. A major metabolite of BCP in bile was N-glucuronide. The cumulative amounts of BCP and BCP-NG in the bile over 8 h were approximately 2.4 +/- 1.4% and 12.6 +/- 2.3% of the dose, respectively. BCP and BCP-NG in the urine were 2.7 +/- 0.7% and 3.2 +/- 0.3% of the dose. Although BCP had a long half-life (over 8.5 h), the preliminary pharmacokinetic parameters (0-8 h) were determined: t 1/2, 8.52 +/- 1.96 h; AUC, 419.9 +/- 45.2 microg x h/ml; MRT, 3.29 +/- 0.11 h; CLtot, 5.93 +/- 0.54 ml/h; and Vdss, 19.5 +/- 1.3 l. These observations are the first pharmacokinetic findings for the N-glucuronide of the barbituric acid derivatives.
authors.affiliation: Department of Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan. k-mohri@my-pharm.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Mohri
authors.forename: Y
authors.initials: Y
authors.lastname: Uesawa
authors.forename: T
authors.initials: T
authors.lastname: Uesugi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000652:urine; D001463:Barbiturates / Q000493:pharmacokinetics* / Q000652:urine; D001659:Biliary Tract / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism* / Q000652:urine; D006207:Half-Life; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001463:Barbiturates; D020719:Glucuronides; C084817:bucolome