METABOLISM OF PENTAERYTHRITOL TRINITRATE AND PENTAERYTHRITOL BY DOGS

¹ Biochemistry Department, Warner-Lambert Research Institute, Morris Plains, New Jersey

The purpose of this study was to determine the metabolic profile of pentaerythritol trinitrate, a relatively soluble organic nitrate with hypotensive activity. Three dogs were given 10 mg of encapsulated C¹⁴-pentaerythritol trinitrate per kg b.wt. Drug absorption and excretion were rapid. The peak blood radioactivity was observed at two hours postadministration when 6.8% of the administered C¹⁴ was in the systemic circulation. Forty-eight hours after dosing, very small quantities of C¹⁴ were found in the heart, kidney, lung, liver, spleen and fat, whereas 88% of the C¹⁴ dose was present in the urine and 10% in the feces. Unaltered pentaerythritol trinitrate was detected in three blood specimens; none was found in the urine or feces. The major metabolites were pentaerythritol dinitrate and pentaerythnitol mononitrate in the blood, pentaerythritol mononitrate and pentaerythnitol in the urine and pentaerythritol in the feces. After administering a single p.o. dose of C¹⁴-pentaerythritol to one dog, the compound was found to be quickly absorbed and excreted unchanged.