Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling.

摘要: The relationships between plasma or brain concentrations and analgesic effects of both buprenorphine (BN) an active metabolite, norbuprenorphine (NBN), were investigated in rats. Maximal measured by a tail flick test obtained at 10 30 min after intravenous (i.v.) administration BN (8 micrograms/kg dose) NBN (100 dose), respectively. No correlation was observed effect the early concentrations. However, latency times, concentration plasma, cerebellum rest (including brainstem, midbrain cerebrum) related counterclockwise hysteresis fashion to analgesia. There no relationship estimated specific binding effects. After i.v. NBN, approximately one-fiftieth that BN. n-octanol/water partition coefficient one-tenth Further, results intraventricular each drug suggested intrinsic activity one-fourth From these findings, we conclude remarkably weak pharmacological may be due not only low permeability into but also its small effect.