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Sodium Dependence of Nitrofurantoin Active Transport Across Mammary Epithelia and Effects of Dipyridamole, Nucleosides, and Nucleobases

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Abstract

Purpose. The sodium dependence and effects of nucleoside and nucleobase transport inhibitors were determined to ascertain the role of sodium dependent nucleoside or nucleobase transporters in nitrofurantoin active transport across mammary epithelia.

Methods. Five lactating female rats received steady-state intravenous infusions of nitrofurantoin with and without the broad-based inhibitor dipyridamole. In the CIT3 murine model of lactation, 14C-nitrofurantoin basolateral to apical permeability was examined in the presence of varying sodium concentrations, purine and pyrimidine nucleosides and nucleobases, and dipyridamole.

Results. Dipyridamole effectively inhibited 14C-nitrofurantoin flux across CIT3 cells, with Ki = 0.78 μM (95% C.I. = 0.11 to 5.3 μM) and significantly decreased the milk-to-serum ratio of nitrofurantoin from 29.2 ∓ 5.0 to 11.0 ∓ 6.3 without changing systemic clearance. Nitrofurantoin active transport was significantly inhibited by complete sodium replacement. Adenosine and guanosine significantly inhibited nitrofurantoin permeability (54.5 ∓ 2.6 (μl/hr)/cm2 and 50.7 ∓ 0.6 (μl/hr)/cm2, respectively, vs. control 90.5 ∓ 4.6 (μl/hr)/cm2) but uridine, thymidine, and the nucleobases had no effect.

Conclusions. Nitrofurantoin active transport was sodium dependent and inhibited by dipyridamole, adenosine, and guanosine, but known sodium dependent nucleoside or nucleobase transporters were not involved.

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Authors and Affiliations

  1. Division of Pharmaceutical Science, University of Kentucky College of Pharmacy, Lexington, Kentucky, 40536-0082

    Phillip M. Gerk & Patrick J. McNamara

  2. Department of Physiology, University of Colorado Health Science Center, Denver, Colorado, 80262

    Linda Hanson & Margaret C. Neville

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  1. Phillip M. Gerk
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  2. Linda Hanson
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  4. Patrick J. McNamara
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Correspondence to Patrick J. McNamara.

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Gerk, P.M., Hanson, L., Neville, M.C. et al. Sodium Dependence of Nitrofurantoin Active Transport Across Mammary Epithelia and Effects of Dipyridamole, Nucleosides, and Nucleobases. Pharm Res 19, 299–305 (2002). https://doi.org/10.1023/A:1014495018640

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