USE OF PHOSPHONOCARBOXYLIC ACIDS AS INHIBITORS OF SODIUM-PHOSPHATE COTRANSPORT

Phosphonocarboxylic acids, initially developed as antiviral agents, ar e found to be specific inhibitors of phosphate CPS transport across ce ll membranes. Foscarnet (PFA), the most potent and the most widely use d compound, can induce phosphaturia both after parenteral and oral adm inistration. Furthermore, it can inhibit intestinal phosphate absorpti on when administered orally. PFA absorption and bioavailability are in creased in animals on phosphate restricted diets. PFA also blunts the adaptive increase in intestinal and renal Na+-P-i cotransport which ac companies dietary phosphorus restriction. Finally, PFA is shown to inh ibit hydroxyapatite crystal formation and calcium phosphate precipitat ion when tested in in vitro systems. These properties, and the low tox icity of PFA, point to potential new applications for PFA and some of its analogs in clinical conditions such as chronic renal insufficiency , where phosphate retention may lead to progression of renal failure a nd to other serious complications.