Abstract
This report describes the distribution, excretion and fate of 5-HP- 14C in normal CDF 1 male mice. After a single ip dose of 400 mg 5-HP- 14C/kg, maximum localization of the drug in tissues and blood occurred within 10 minutes, followed by a rapid loss of radioactivity, so that after 24 hours the drug could not be detected in tissues or blood. The biological half-life of 5-HP in blood was estimated to be 15 minutes. Approximately 80% of the 14C in the administered dose was excreted by the kidneys, and of this amount only 16 to 20% was in the form of unchanged drug, indicating that extensive metabolism had occurred. After a multiple-dose regimen, the drug was retained by various tissues for a more extended period. In 96 hours about 3 and 10% of the total radioactivity could be attributed to free drug in spleen and blood, respectively. The antileukemic effectiveness of 5-HP in a multiple-dose regimen on Days 1, 5, and 9 may be explained in part by these observations. The major urinary metabolite of 5-HP was shown to be a glucuronide conjugate although other unidentified biotransformation products were also detected in urine.
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