Studies on 3-chloro-4-methyl-(4-14C)-7-hydroxycoumarin in rats.

The distribution, excretion and biotransformation of 3-chloro-4-methyl-(4-14C)-7-hydroxycoumarin [(14C) chlorferron] were studied in the rats after single oral administration. Male and female Wistar rats were given single oral doses of 0.5 and 20.0 mg/kg body weight of (14C) chlorferron and routes and rates of elimination of 14C activity were followed for 7 days. Following administration of 20 mg/kg, 96.74 +/- 3.68% and 94.98 +/- 6.15% of the dose were excreted by male and female rats, respectively. The excretion of total radioactivity after 0.5 mg/kg was significantly (P less than 0.05) higher in male rats (93.77 +/- 2.27%) as compared to female rats (87.23 +/- 1.96%). Approximately 80-90% of the excreted radioactivity was detected in urine. Analysis of urine showed no qualitative difference in the biotransformation pattern of (14C) chlorferron in male and female rats. (14C) chlorferron derived metabolites were excreted in both conjugated and unconjugated forms. After 7 days of dosing, very low concentrations of (14C) chlorferron derived residues were detected in different body tissues. No detectable sex difference in body distribution of radioactivity was observed. These results suggest that (14C) chlorferron is rapidly eliminated from the body and only small amounts are stored in the organs.