塩酸モルヒネ坐剤(第1報)ラットにおけるバイオアベイラビリティ

Abstract

Bioavailabilities of morphine after rectal administration of three different morphine-HCl suppositories (5 mg/kg) were evaluated in rats. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The plasma and brain concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine.HCl solution (5 mg/kg). The plasma levels of morphine after rectal administration of morphine.HCl solution were higher than those after oral administration, whereas the plasma levels of metabolite, morphine-3-glucuronide was lower than those after oral administration. Morphine after rectal administration of Witepsol H-15 suppository released more easily than other suppositories. The inter-animal variation in the plasma levels of morphine after rectal administration of Witepsol H-15 suppository was smaller than those of other suppositories. Results obtained in this study indicate that morphine.HCl suppository prepared with Witepsol H-15 is a promising material as preparation of suppositories.