Abstract
Nitrofurantoin and other agents are actively transported into human and rodent milk. The purpose of this study was to determine whether nitrofurantoin active transport across mammary epithelia occurs basolaterally or apically, using the CIT3 cell culture model of lactation. The CIT3 model actively transports nitrofurantoin in the basolateral to apical direction. Basolateral to apical permeability [92.9 ± 6.6 (μl/h)/cm2] was differentially decreased by unlabeled nitrofurantoin (250 μM) on the basolateral, apical, or both sides [49.5 ± 1.8, 57.9 ± 1.4, or 48.5 ± 1.6 (μl/h)/cm2, respectively]. Apical to basolateral permeability [27.6 ± 1.8 (μl/h)/cm2] was increased in the presence of unlabeled nitrofurantoin (250 μM) on the basolateral, apical, or both sides [36.4 ± 1.5, 39.9 ± 0.7, 42.4 ± 1.1 (μl/h)/cm2, respectively]. These data indicate a basolateral active uptake mechanism for nitrofurantoin, which remains to be identified. This mechanism may influence the exposure of suckling infants to xenobiotics, as well as having potentially toxic effects on the lactating mammary epithelium and possibly altering the nutritional quality of the milk.
Footnotes
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↵ 1 Abbreviations used are: B, basolateral; A, apical; Pe, permeabilities; J, flux; Cd, 14C-nitrofurantoin concentration on the donor side; ANOVA, analysis of variance.
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This work was supported by the University of Kentucky Women's Health Initiative and National Institutes of Health Grant HD37463.
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This work was published as a part of P. M. G.'s doctoral dissertation at the University of Kentucky. These results were presented in part at the annual meeting of the American Association of Pharmaceutical Scientists in 2000.
- Received September 18, 2002.
- Accepted February 24, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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