COMPARATIVE PHARMACOKINETICS AND PHARMACODYNAMICS OF REMIFENTANIL, ITS PRINCIPLE METABOLITE (GR90291) AND ALFENTANIL IN DOGS

Remifentanil is an esterase-metabolized opioid developed for use in an esthesia. The principal metabolite of remifentanil, GR90291, is consid ered to be less potent. This study determined the relative potency of GR90291 and alfentanil, compared with remifentanil, in anesthetized do gs. Male dogs received thiamylal sodium, and anesthesia was maintained using isoflurane and N2O in oxygen. Each dog received a 5-min infusio n of 0.5 mu g/kg/min remifentanil, 500 mu g/kg/min GR90291 and 1.6 mg/ kg/min alfentanil in random order, separated by 1 week. Serial blood s amples were collected during and after the infusion. The electroenceph alogram was evaluated using aperiodic analysis. The pharmacokinetics a nd pharmacodynamics of remifentanil, GR90291 and alfentanil were deter mined using nonlinear least-squares regression analysis. Remifentanil was rapidly eliminated, with a terminal half-life of 6 min, compared w ith 19 min for GR90291 and alfentanil. Using the estimated concentrati on that elicits 50% of the maximum response (EC50) for delta EEG activ ity and spectral edge(95), remifentanil was 4213 to 4637 times more po tent than GR90291 and 7.7 to 8.5 times more potent than alfentanil. Th e blood-brain equilibration half-life was 2.3 to 5.2 min for remifenta nil, 0.39 to 0.41 min for GR90291 and 3.1 to 3.7 min for alfentanil.