• 1 January 1995
    • journal article
    • Vol. 272  (1) , 242-7
Abstract
New findings are presented on the specific transport mechanisms of foscarnet (trisodium phosphonoformate hexahydrate) in rat small intestinal tissue and proof for the partial participation of the Na(+)-phosphate co-transport system in foscarnet transport. The transport of the free acid form of foscarnet, phosphonoformic acid (PFA), was studied in rat small intestine by applying Ussing chambers. Transport studies in both mucosal (m)-to-serosal (s) and s-to-m directions revealed polarization of PFA transport. In m-to-s studies, nonlinear concentration-dependent transport was observed and described by the following transport parameters (estimate +/- asymptotic standard error): 0.84 +/- 0.13 mumol/h.cm2, 1.13 +/- 0.29 mM and 0.22 +/- 0.05 cm/h for the maximal transport rate (Jmax), the half-maximal transport concentration (Kt) and the passive membrane permeability constant (Pm), respectively. PFA transport (1.0 mM) was reduced to 72% and to 56% in the presence of the structural analogs phosphate and arsenate (10 mM), respectively. Bidirectional transport studies of PFA at 38 degrees C and 4 degrees C revealed a higher decrease in transport rate for the m-to-s studies than for the s-to-m studies. The combined results of the experiments described in this study demonstrate that PFA transport across rat small intestine is partly passive, using both the paracellular and transcellular pathways, and partly carrier-mediated, involving the phosphate co-transport system.

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