Abstract

In order to evaluate the first-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, intravenous 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 intravenous and oral administration. Route of administration had no affect on plasma half-life (about 115 minutes) 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 intravenous administration. It can be estimated that approximately two-thirds of the overall first-pass effect (82%) of morphine is due to extraction and/or metabolism in the intestine and the remaining one-third by the liver.