KINETICS OF THE DECARBOXYLATION OF FOSCARNET IN ACIDIC AQUEOUS-SOLUTION AND ITS IMPLICATION IN ITS ORAL ABSORPTION

The kinetics of decarboxylation of the antiviral foscarnet (trisodium phosphonoformate) to form carbon dioxide and phosphorous acid was studied in aqueous solutions at 37°C over the pH range 0.2-3.6, using a direct spectrophotometric method as well as an HPLC procedure. The variation of the rate of degradation with pH could be accounted for in terms of a spontaneous decarboxylation of the undissociated acid form of foscarnet with a first-order rate constant of 0.10 min-1. Half-lives for the degradation were 29 min, 231 min and 51 h at pH 1, 2 and 3, respectively. It was estimated that in the gastric pH range 1-2 and with a gastric emptying half-time of 50 min, 18-63% of an ingested dose would be decomposed in the stomach. It is concluded that intragastric degradation may be of significance for the absorption of foscarnet upon peroral administration. © 1990.