Excretion and distribution of thiazesim-14C with its biotransformation in vivo and in vitro

✍ Scribed by J. Dreyfuss; J. R. Swoap; C. Chinn; S. M. Hess

• Publisher: John Wiley and Sons
• Year: 1968
• Tongue: English
• Weight: 838 KB
• Volume: 57
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600570906

✦ Synopsis

Thiaze~im-1~C [5-(2-dimethylaminoethyl) -2,3dihydro -2henyl -1,5benzothiazepin-4 (5H)-one] was demonstrated to have been compEtely absorbed after administration to rats. After an i.p. dose of 30 mg. of thiazesimJC per kg. the drug was found in all the tissues that were examined; it was most concentrated in the livers, lungs, and kidneys. The half-life in the brains was about 2 0 min. The drug was converted in the rat to three major metabolites, two of which were resent in unconjugated form and also as sulfate and glucuronide conjugates. Uncganged thiazesimJ4C and the three metabolites accounted for 68 and 59 percent of the radioactivity in rat urine and feces, respectively, in the tirst 24 hr. after administration. More than 90 percent of an oral dose was excreted by rats or by dogs in 3 days; the agent was completely eliminated in 4-6 days. Thiazesim-14C was metabolized by a microsomal enzyme system derived from rat liver. The system re uired oxygen, NADPH, and nicotinamide. Two major products were obtained %y the incubation of the drug with rat liver preparations in vitro; they were absent in the excreta of treated rats. Metabolism of thiazesirn-l4C by liver preparations from the dog, cat, or rabbit was also examined. Although the metabolites appeared to have been similar in all the species examined, the preparations obtained from rat livers metabolized thiazesim-W twice as fast as microsomes obtained from the other species.