Pharmacokinetic studies of 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone ethanolamine salt(Hoe 296) in rats

Rats were dermally treated with 1% 14C-6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone ethanolamine salt (Hoe 296) solution in polyethyleneglycol-400 in doses of 10 mg/kg, and the distribution, metabolism and excretion were studied. Radioactivity began to appear in the blood after 1 hour and peaked at 6 hours after the drug application. The radioactivity in the blood then declined and was hardly detectable 7 days after the application. The radioactivity in the organs also peaked 6 hours after the application. The levels of the radioactivity in the spleen, adrenal, kidney, stomach, liver and thyroid of both sexes, and in the small intestines of females were higher than those in other organs. The radioactivity in each organ, however, could hardly be detected in either males or females 21 days after the drug application. Urinary and fecal excretion of 14C-Hoe 296 peaked 2 days after the application, and the radioactivity in the urine and feces was barely detectable 21 days after the application. A total 11.43% of the applied dose was excreted in both the urine and feces in males, and a total of 12.35% in females. The ratio of urinary excretion to fecal excretion was approximately 5:1. Using the technique of thin-layer chromatography, no metabolite in the urine could be detected. (author)