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Journal of Pharmacology And Experimental Therapeutics, Vol. 150, Issue 3, 484-490, 1965
Copyright © 1965 by American Society for Pharmacology and Experimental Therapeutics

ABSORPTION, DISTRIBUTION AND EXCRETION OF AMANTADINE HYDROCHLORIDE

W. E. Bleidner 1, J. B. Harmon 1, W. E. Hewes 1, T. E. Lynes 1, and E. C. Hermann 1

1 Pharmaceutical Research Division, Industrial and Biochemicals Department, E. I. du Pont de Nemours and Company, Inc., Wilmington, Delaware

A sensitive and specific gas chromatographic method is described for determining amantadine, a recently discovered antiviral drug, in body fluids and tissues.

Studies of the drug dynamics and metabolic fate of amantadine in mice, rats, dogs, monkeys and man are reported. There is no evidence for metabolism of the drug in man. The monkey and the mouse appear to metabolize it less than the other animals and most nearly approximate man. The urine appears to be the major route of elimination. The dog has been shown to convert a portion of the administered drug to its N-methyl derivative which is excreted in the urine.

Amantadine hydrochloride is well absorbed by the oral route in all species studied and exhibits a fairly long half-life as measured by excretion rate. The rate of excretion of the drug is first order.

The excretion pattern in man that results from multiple dosage is consistent with predictions made from single dose experiments.

Accepted on June 24, 1965




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