Use of phosphonocarboxylic acids as inhibitors of sodium-phosphate cotransport.
Phosphonocarboxylic acids, initially developed as antiviral agents, are found to be specific inhibitors of phosphate (P(i)) transport across cell membranes. Foscarnet (PFA), the most potent and the most widely used compound, can induce phosphaturia both after parenteral and oral administration. Furthermore, it can inhibit intestinal phosphate absorption when administered orally. PFA absorption and bioavailability are increased in animals on phosphate-restricted diets. PFA also blunts the adaptive increase in intestinal and renal Na(+)-P(i) cotransport which accompanies dietary phosphorus restriction. Finally, PFA is shown to inhibit hydroxyapatite crystal formation and calcium-phosphate precipitation when tested in in vitro systems. These properties, and the low toxicity 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 and to other serious complications.
Loghman-Adham
M
M
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132, USA.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism; D017245:Foscarnet / Q000031:analogs & derivatives / Q000494:pharmacology*; D007408:Intestinal Absorption; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D010710:Phosphates / Q000097:blood / Q000652:urine; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D000998:Antiviral Agents; D002130:Calcium Phosphates; D002352:Carrier Proteins; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D017245:Foscarnet