Add time:07/25/2019         Source:sciencedirect.com

The absorption, biotransformation, and excretion of pentaerythritol tetranitrate was studied after oral administration of two dosages, 20 and 40 mg., to patients. The drug was given as 14C-pentaerythritol tetranitrate incorporated into tablets of a type used clinically. The total 14C excretion in 48 hr. was approximately 92% of both doses. However, a greater proportion of the lower dose was excreted in the urine: 60% of the 20-mg. dose and 50% of the 40-mg. dose. Drug radioactivity was detected in the blood within 15 min., and peak levels occurred from 4 to 8 hr. after administration. The only radioactive compounds found in the blood were pentaerythritol, pentaerythritol mononitrate, and pentaerythritol dinitrate. These drug metabolites were also present in the urine and feces. The kinetics of renal excretion of the principal urinary metabolites, pentaerythritol and pentaerythritol mononitrate, were first order. The renal elimination-rate constant, ke, of pentaerythritol was independent of the dose, but ke for pentaerythritol mononitrate was dose related and significantly smaller for the higher dose. The ratio of pentaerythritol mononitrate/pentaerythritol excreted in the urine was approximately 1:1 for the lower dose and 3:1 for the higher dose. The findings indicate a rapid deesterification of pentaerythritol tetranitrate by the human to pentaerythritol mononitrate after oral ingestion, but a limited capacity for the conversion of pentaerythritol mononitrate to pentaerythritol.

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