关键词: 灵仙新苷, LC-MS/MS, 药动学, 绝对生物利用度, Beagle犬

Abstract: AIM: To investigate the pharmacokinetics and absolute bioavailability of clematichinenoside AR (C-AR) in Beagle dogs. METHODS: By applying four cycle crossover design, a single dose of C-AR was administrated (i.v. 0.75 mg/kg or i.g. 7.5, 15 or 30 mg/kg) to 8 Beagle dogs.Blood samples were collected before and at different intervals after C-AR administration. The concentration of C-AR in dog plasma was determined by LC-MS/MS method.The pharmacokinetic parameters were estimated by DAS 2.0 pharmacokinetic program,and the absolute bioavailability was calculated.RESULTS: After single dose ig of 7.5, 15 and 30 mg/kg C-AR, the pharmacokinetics parameters were estimated as follows: t_1/2: (14.3±2.7), (13.3±1.3) and (13.7±2.4) h; AUC_0-36: (1.9±1.2), (4.5±1.9) and (8.0±3.3) μg·h·mL^-1; C_max: (0.14±0.08), (0.27±0.10) and (0.52±0.28) μg/mL. After single dose i.v. of 0.75 mg/kg C-AR, the pharmacokinetics parameters were estimated as follows: t_1/2: (13.3±3.0) h,AUC_0-36:(66.2±12.8) μg·h·mL^-1. The absolute bioavailability of C-AR following i.g. administration was 0.32%, 0.35% and 0.30%. CONCLUSION: The absolute bioavailability of C-AR in dogs is low, and the pharmacokinetic properties were linear in Beagle dogs.

Key words: Clematichinenoside AR, LC-MS/MS, Pharmacokinetics, Absolute bioavailability, Beagle dog