Abstract
Summary
The T 1/2 of DDS ranged from 2 to 4 hr in male and female BALB/c and in male B6C3F1 mice. It was independent of strain or sex. The T 1/2 of MADDS could not be measured because of minimal acetylation of administered DDS and nearly complete deacetylation of administered MADDS. Thus, mice are poor acetylators of DDS and very efficient deacetylators of MADDS. Studies in vitro showed that mouse plasma deacetylated MADDS and DADDS but at a rate insufficiently rapid to account for the observed deacetylation of MADDS in vivo. Examination of the binding of DDS and MADDS to plasma proteins both in vivo and in vitro showed considerable binding of both compounds, as is the case in man.
The disposition of DDS in the mouse is much different from that in man. Although one may apply some information from studies in the mouse to the clinical use of DDS in the treatment of human leprosy, many therapeutic variables important to human treatment cannot be meaningfully studied in the mouse.
The authors gratefully acknowledge the assistance of Donna C. Ghoul, John F. Murray, Jr., and Anne K. Uher in the studies reported here.
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