The antinociceptive effect and pharmacokinetics of olvanil following oral and subcutaneous dosing in the mouse.

Mice were tested for response latency on a 55 degrees C hot plate after subcutaneous (S.C.) or oral administration of olvanil (dose level 200 and 300 mg/kg, respectively). Only the S.C. injection of olvanil produced antinociception. A pharmacokinetics experiment with radiolabeled olvanil (200 mg/kg) was conducted to determine whether this antinociception difference was related to a difference in plasma concentration of olvanil following the two routes of administration. The results indicate that concentrations of radioactivity (olvanil plus metabolites) in plasma reach a peak higher and faster after oral dosing than after S.C. injection. However, the area under the concentration-time curve (AUC) for recovery of radioactivity was slightly higher after the S.C. injection than after the oral dose of olvanil. In contrast, intact olvanil is barely measurable (10 to 30 ng/g) in plasma following an oral dose but is present in high concentration (100 to 2000 ng/g) following S.C. injection. The AUC for olvanil was also higher following a S.C. dose. These data indicate that olvanil fails to produce antinociception after oral dosing in mice not due to lack of absorption, but because it undergoes first pass metabolism.