Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.751796
Title: Some aspects of the metabolism and disposition of tiquinamide in several animal species
Author: Pierce, David M.
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1980
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Abstract:
Tiquinamide, 5,6,7,8-tetrahydro-3-methylquinoline-8-thiocarboxamide, is a novel tetrahydroquinoline structure with gastric anti-secketory properties. This thesis describes its metabolism and disposition in rat, patas monkey and man. Gastric absorption was found in anaesthetized, pylorus-ligated patas monkeys, but occurred inconsistently in conscious animals studied by a novel mixed isotope method. Tiquinamide did not significantly alter the rate of gastric emptying in the patas monkey. Metabolic studies in the rat, patas monkey and man revealed that w-oxidation of the 3-methyl group to the corresponding carboxylic acid was a common pathway in all three species, as was allylic hydroxylation resulting in a 5-hydroxylated product which was subsequently conjugated with glucuronic acid. Desulphuration of the thioamide group to the nitrile occurred by chemical/ metabolic means. Aromatization of the saturated ring occurred in the rat and man, but not in the patas monkey. Some quantitative species differences were also found. Plasma kinetic studies revealed that tiquinamide was rapidly absorbed and eliminated. However, metabolites were more quickly excreted in patas monkey and man than in the rat. An unidentified metabolite constituted the outstanding component in rat plasma during the slow elimination phase. Tissue distribution studies revealed no major depots from which slow delivery could have occurred. However, tissue uptake and gastric recycling, resulting in high stomach concentrations, may have been factors contributing to slow elimination in the rat. Rapid urinary excretion occurred in patas monkey and man, whereas a slower phase predominated in the rat. The difference was attributed to the more extensive formation of water-soluble 3-carboxylic acids and glucuronides in the former species. Faecal excretion was extensive only in the rat. No evidence of entero-hepatic circulation was observed. Factors contributing to the species difference in elimination are reviewed. The significance of the metabolism and disposition of tiquinamide for its development as ananti-secretory agent is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.751796  DOI: Not available
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