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The relationship between the pharmacokinetics and the pharmacodynamics of eptazocine, a narcotic-antagonist analgesic, was investigated in rats. The analgesic effect of eptazocine (2.5, 5 and 10 mg/kg) following intravenous (i.v) administration was evaluated by both the Randall-Selitto method and the D'Amour-Smith method. The analgesic effects were determined before and at designed intervals for a period of 120 min after eptazocine administration, and are expressed as area under the effect-time curve (AUC(E)). The plasma concentration of eptazocine was determined by fluorescence HPLC and was analyzed with a two compartment open model using the nonlinear least-squares method. Eptazocine produced a dose-dependent analgesic effect. It was demonstrated that eptazocine has a linear relationship between AUC(E) and the area under the plasma concentration-time curve (AUC) following i.v. administration for three different doses ranging from 2.5 to 10 mg/kg.

Pharmacokinetic/Pharmacodynamic Relationship of Eptazocine, a Narcotic-Antagonist Analgesic, in Rats.