Abstract
Drug disposition of chlormezanone-14C and its interaction with aspirin were studied in mice. Chlormezanone-14C was well and rapidly absorbed from the gastrointestinal tract after oral administration of 24mg/kg. Blood levels of radioactivity reached a peak 60 min later. Tissue concentration became lower in the order of the adrenal gland, kidney, liver, pituitary, lung, brain and muscle. The high affinity of chlormezanone-14C for the tissues was deduced from the fact that the concentration ratio of tissue to blood was larger than 1.0. Urinary excretion of radioactivity was approximately 21% of the administered dose within 120min. Examination of metabolites in the plasma, liver, kidneys and brain indicated that chlormezanone-14C was mainly found in the tissues in an unchanged form but its metabolites such as p-chlorobenzoic acid, p-chlorohippuric acid, N-methyl-p-chlorobenzamide, 2-[N-methyl-N-(p-chlorobenzoyl)] carbamoylethylsulfonic acid and p-chlorobenzoic acid glucuronides showed a low concentration. Aspirin administered concomitantly had no effect on the absorption, distribution and metabolism of chlormezanone-14C, but significantly inhibited urinary excretion of chlormezanone-14C and its metabolites. These results suggest that chlormezanone-14C is well and rapidly absorbed and is distributed highly into tissues without the effect of combination of aspirin and exerts its pharmacological effect in an unchanged form.
