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Further Investigation of Amantadine Disposition: Acetylation and Secretion

Amantadine is a cationic aliphatic primary amine eliminated by the kidneys, excreted predominantly unchanged into the urine, and undergoes limited metabolism. Renal tubule secretion has an important role in its elimination. We studied two aspects of amantadine disposition, firstly acetylation, by developing a model to induce the enzyme spermidine/spermine N1-acetyltransferase (SSAT1) with
N1, N11-diethylnorspermine (DENSPM) and alcohol (Alc) as representative agents reported to induce its activity, and secondly renal secretion, by studying the effect of intravenous bicarbonate infusion on its renal elimination. We drew two conclusions, firstly, longer exposure to Alc combined with DENSPM administration provided the greatest potentiation of SSAT1 enzyme activity than each agent alone, which indicates a high likelihood of synergy between Alc and DENSPM; and secondly, bicarbonate load administered to healthy male volunteers impairs amantadine renal secretion in the absence of a clinically important change in blood pH, serum creatinine concentration or urinary creatinine clearance.

Identiferoai:union.ndltd.org:MANITOBA/oai:mspace.lib.umanitoba.ca:1993/3937
Date08 April 2010
CreatorsFatani, Solafa
ContributorsSitar, Daniel (Pharmacology and Therapeutics), Hatch, Grant (Pharmacology and Therapeutics) McNicol, Archie (Dentistry)
Source SetsUniversity of Manitoba Canada
Languageen_US
Detected LanguageEnglish

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