1ST-PASS EFFECT OF MORPHINE IN RATS

Abstract

To evaluate the 1st-pass effect of morphine, the pharmacokinetic parameters of 3H-morphine (5 mg/kg) were studied in male Sprague-Dawley rats by comparing the plasma concentrations after oral, i.v. and intraportal administration. Morphine was almost completely absorbed from the gastrointestinal tract, since no significant difference was found in the cumulative urinary excretion of radioactivity after i.v. and oral administration. Route of administration had no effect on plasma half-life (about 115 min) of unchanged morphine. In contrast, the area under the plasma concentration vs. time curve for morphine after oral administration was only about 18%, and after intraportal administration about 40% of that observed after i.v. administration. Approximately 2/3 of the overall 1st-pass effect (82%) of morphine was probably due to extraction and/or metabolism in the intestine and the remaining 1/3 by the liver.