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 intestina l 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, follo wed by administration of an oral bolus of [C-14]PFA (100 mg/kg). Of th e 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 mu g/mL, respectively). [C-14]PFA uptake, determined in intestinal BBM vesicles (BBMV), was Na+ gradient (Na-out(+) > Na-in (+)) dependent. Dietary phosphorus restriction resulted in a 39.8% inc rease in the initial (1 min) Na+-dependent [C-14]PFA uptake by intesti nal BBMV. We conclude that PFA absorption is enhanced by dietary phosp horus restriction.