ABSORPTION, EXCRETION AND METABOLISM OF PENTA-ERYTHRITOL TETRANITRATE BY HUMANS

¹ Departments of Pharmacology and Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina; Department of Biochemistry, Warner-Lambert Research institute, Morris Plains, New Jersey

Ten men, 5 with ischemic heart disease and 5 healthy volunteers, were administered 20-mg Peritrate tablets containing C¹⁴-labeled pentaerythritol tetranitrate and were restricted to a clinical research unit for the collection of blood, urine and feces. The control and coronary groups exhibited no significant difference in their absorption, excretion and biotransformation of the drug. Virtually all [94.5 ± 1.5% (S.E.)] of the radioactivity was recovered from 9 subjects; the other subject was unable to provide complete fecal excretion because of an impaction. For the 10 men, the mean urinary excretion was 53.1 ± 3.4% in 24 hours and 60.3 ± 3.6% in 48 hours, and the mean fecal excretion was 31.5 ± 4.8% in 72 hours. Radioactivity was found in the blood within 15 minutes after dosing. Peak blood radioactivity was sustained over the period from 4 to 8 hours after dosing and represented approximately 5.6% of the radioactivity administered. The blood level of radioactivity declined slowly to about 40% of the maximum at 24 hours and to 10% at 48 hours. The blood, urine and feces collections were assayed for pentaerythritol tetranitrate and its de-esterified metabolites by thin-layer chromatography and radioscanning. pentaerythritol tetranitrate was found consistently in the feces, rarely in the urine, but not in the blood. Pentaerythritol trinitrate was found only in two fecal specimens. Significant levels of pentaerythritol dinitrate were present in the blood from 30 minutes to 4 hours after drug administration, and small quantities were detected in occasional urine and feces collections. The principal drug metabolites were pentaerythritol mononitrate and pentaerythritol.