Abstract
Nitrofurantoin is a commonly used urinary tract antibiotic that has been found at high concentrations in human milk. In vivostudies in rats were carried out to determine the mechanism by which this drug crosses the mammary epithelium. Lactating rats were gavage-fed with nitrofurantoin, and their milk and plasma levels of the antibiotic were measured at intervals up to 8 hr. The average milk-to-plasma (M/P) ratio, calculated from the areas under the milk and plasma curves, respectively, was 23 compared with a ratio predicted to be about 0.3 on the basis of lipid partitioning and protein binding determinations. M/P ratios for two nitrofurantoin congeners were also calculated. The neutral compound furazolidone had a M/P ratio of about 1, as predicted, whereas the basic compound furaltadone had a M/P ratio of 3.49 compared with a predicted ratio of 1.4. These data suggest that nitrofurantoin and, to a lesser extent, furaltadone are actively transported across the mammary epithelium into milk.
Footnotes
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Send reprint requests to: Frank W. Kari, National Institute of Environmental Health Sciences, Mail Drop B3-09, P.O. Box 12233, Research Triangle Park, NC 27709.
- Abbreviations:
- M/P ratio
- milk-to-plasma ratio
- S/W ratio
- skim-to-whole ratio
- Received May 24, 1996.
- Accepted November 13, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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