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Enhanced bioavailability of phosphonoformic acid by dietary phosphorus restriction
M Loghman-Adham1, G T Motock, M Levi
1Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Abstract:
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.
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