Enhanced bioavailability of phosphonoformic acid by dietary phosphorus restriction.
Phosphonoformic acid (PFA, foscarnet) is a potent inhibitor of Na(+)-P(i) cotransport in intestinal and renal brush border membranes (BBM). We have studied the effect of dietary phosphorus restriction on intestinal PFA absorption and bioavailability. Rats were placed on low (0.04% P(i), LPD) or normal (0.95% P(i), NPD) phosphorus diets for 5 days, followed by administration of an oral bolus of [14C]PFA (100 mg/kg). Of the oral PFA dose, 60 +/- 4% was absorbed in LPD rats, compared with 43 +/- 3% in NPD rats (P < 0.05, N = 5). This was associated with higher plasma PFA concentrations in LPD compared with NPD rats (44.2 +/- 2.0 and 17.9 +/- 4.3 micrograms/mL, respectively). [14C]PFA uptake, determined in intestinal BBM vesicles (BBMV), was Na+ gradient (Na+out > Na+in) dependent. Dietary phosphorus restriction resulted in a 39.8% increase in the initial (1 min) Na(+)-dependent [14C]PFA uptake by intestinal BBMV. We conclude that PFA absorption is enhanced by dietary phosphorus restriction.
Loghman-Adham
M
M
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Motock
G T
GT
Levi
M
M
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001682:Biological Availability; D002352:Carrier Proteins / Q000378:metabolism; D004032:Diet; D017245:Foscarnet / Q000008:administration & dosage / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D010758:Phosphorus / Q000008:administration & dosage* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D010758:Phosphorus; D017245:Foscarnet