[Morphine hydrochloride suppositories. II. Bioavailability of morphine hydrochloride suppositories in dogs].

Bioavailabilities of morphine after rectal administration of three different morphine.HCl suppositories were evaluated in dogs, whose rectum was lavaged or non-lavaged. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The release of morphine from the suppositories was examined after stored for two weeks at 30 degrees C. The plasma 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. In the case of rectal lavaged dogs, the plasma levels of morphine after rectal administration of morphine.HCl solution were higher than those after oral administration of morphine.HCl solution. The release of morphine from Witepsol H-15 suppository was more rapid than those from other suppositories. Morphine after rectal administration of Witepsol H-15 suppository was rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller than those of other suppositories. In rectal non-lavaged dogs, the bioavailabilities of morphine after rectal administration of morphine.HCl solution and suppositories decreased more than those of rectal lavaged dogs. Although the bioavailability of morphine after rectal administration of morphine.HCl was decreased by the influence of contents in the rectum, morphine from Witepsol H-15 suppository was more rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller. These results indicate that, among their suppositories, Witepsol H-15 suppository is available for the terminal care of malignant disease.