Abstract
For the purpose of selecting an animal model for the study of the aging effect on the pharmacokinetics of nalbuphine, the pharmacokinetic properties in young and in aged rabbits were reported. Thirty-one healthy New Zealand white rabbits ranging in ages (mean) from three months to 43 months (six three months old, group I; nine eight months old, group II; nine 18 months old, group III; and seven 43 months old, group IV) were included in the study. After intravenous bolus injection of nalbuphine (10 mg kg-1) to each rabbit, plasma samples were collected and analysed for nalbuphine by a high-performance liquid chromatography method. The plasma concentration-time data regarding nalbuphine were successfully fitted to a linear two-compartment open model. The elimination half-life of nalbuphine in rabbits increased significantly with age. Consequently, clearance decreased significantly with age. The parameter AUCO-affinity, which is derived from dose/clearance, increased significantly with age. The effect of aging on the pharmacokinetics of nalbuphine in rabbits is quite similar to that in humans. From the present study, it is concluded that rabbits may be suitable for the study of aging effects on the pharmacokinetics of nalbuphine.
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