Studies on 3-Chloro-4-Methyl-(4-¹⁴C)-7-Hydroxycoumarin in Rats

Abstract

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 < 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.