Studies on [8-¹⁴C]Adenosine-5′-Carboxylic Acid Ethyl Ester: I. Metabolic Fate in the Dog, Rat and Mouse

Abstract

1. [8-¹⁴C]Adenosine-5-carboxylic acid ethyl ester ([8-¹⁴C]ACAEE) when administered orally to the dog and rat was rapidly absorbed. Plasma half-lives of ¹⁴C showed that the drug and/or its metabolites were eliminated from plasma at a rapid rate by the rat and somewhat slower by the dog.

2. Urinary elimination of labelled metabolites by the rat and mouse were complete by 4 days. The dog eliminated the majority of the ¹⁴C-dose by 3 days but slowly excreted the rest of the dose for at least 24 days.

3. Separation of the urinary metabolites on columns of AGI (formate) basic resin and Dowex 50 (H⁺) acidic resin revealed a high degree of similarity in the metabolic patterns of [8-¹⁴C] ACAEE in the dog, rat and mouse. Two metabolites were identified, the major one, accounting for 80–90% total radioactivity, was adenosine-5′-carboxylic acid; the second metabolite, inosine-5′-carboxylic acid, contained 6–16% of the radioactivity.

4. Glusulase was shown to enzymically deaminate adenosine-5′-carboxylic acid into inosine-5′-carboxylic acid.