Abstract-Absorption, distribution, excretion and metabolism after oral administration of IH-labelled metiazinic acid were studied. The administrered radioactivity was excreted through both the urinary and fecal routes. The maximum levels of concen tration in blood and most tissues were shown within 3 hr after dosing. The highest radioactivity was found in the kidney throughout all experiments.Relatively high radioactivity was observed in inflammatory-treated parts in rats. Unchanged compound, metiazinic acid S-oxide and these conjugates were found in urine and feces. Approxi mately 60" of the unchanged form was observed in plasma after 6 hr. Metaizinicacid --(IO-methyl-2-phenothiazinyl) acetic acid is a synthetic anti-in flammatory, antipyretic and analgesic drug which contains a phenothiazine ring.L. Julou (1) reported that metiazinic acid exhibited marked anti-inflammatory ac tivity, which is at least equal to and, in some tests, 2 to 4 times higher than that of phe uvlbutazone, while being 3 times higher to 6 times lower than that of indomethacin .K. Tsurumi et al. (2) confirmed the anti-inflammatory activities of metiazinic acid using various methods and concluded that metiazinic acid is clinically considered to be similar to phenylbutazone or flufenamic acid regarding acute and chronic inflammation. side effects, and in the acute toxicity tests, toxic symptoms were observed to be mainly respiratory inhibition. The LD50 value was 2 times and 1.5 times greater than that of phenylbutazone and flufenamic acid respectively, and that in the subacute toxicity test, no toxic symptoms were obesrved in either sex of treated groups of mice and rats. (8-Chloro-l0-methyl-2-phenothiazinyl) acetic acid, dissolved in 0.1 N-NaOH, was reduced with tritium gas over paradiumcarbon. After removal of labile tritium, the crude pro duct was purified by paper-chromatography using n-butanol saturated with water as de veloping solvent and finally recrystallized from ethanol-water.The specific activity of the product was 310 mCi/m mole (1.14 mCi/mg) and the ra diochemical purity was 99",/ by reversed isotope dilution analysis, over 99 by thin-layer chromatography.The material was diluted with non-labelled metiazinic acid before use. Animals and dosageMale Wistar rats weighing 140 to 160 g and male rabbits weighing 2 to 3 kg, fasted for 121 hr were employed. 3H-Metiazinic acid with a specific activity of 2 .54 10' dpm/mg was suspended in 2°-' ~ acacia and given orally to rats at a (lose of 20 mg/kg in a concentration of 8 mg/ml, and to male rabbits at a dose of 20 mg/kg in a concentration of 25 mg/ml and a dose of 60 mg/kg in a concentration of 75 mg/ml. After administration, animals were fed and given water ad libitum. 19easuremenl o/ rodioactil'itV The radioactivity was measured by a liquid scintillation counter, ALOKA Model LSL-653 with automatic quenching moniter.Blood: After administration of 3H-metiazinic acid in rabbits, a small volume of blood was obtained from the ear-vein, absorbed on the filter paper and burnt by an auto mat...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.