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• W2277683163 abstract "Tripelennamine (Pyribenzamine) which was labeled with C14 in the benzyl methylene carbon was used, in the form of the hydrochloride, in studies aimed at elucidating the distribution, excretion and metabolism of this drug in guinea pigs.Through measurement of radioactivity an account is given of the distribution and concentration of drug-derived compounds in tissues and excretory pathways. One hour after injection, all tissues examined contained radioactivity and one-third to one-half of the C14 was located in excretory pathways.Over 90% of the tripelennamine-radioactivity was eventually excreted in the urine. One hour after injection, however, considerable amounts of C14 were found in intestinal contents as well as in urine. Bile cannulation revealed that tripelennamine metabolites were simultaneously excreted through bile and urine. It is, therefore, postulated that a cycle of elimination through the bile and reabsorption from the intestine functions, but that, since metabolites are simultaneously also being excreted in the urine, excretion in the urine becomes the final and main pathway of elimination.Solvent partition, chromatographic examination, absorption spectra, paper electrophoresis and determination of antihistaminic activities were used in characterizing the radioactive excretion products in the urine. Several radioactive compounds were present in the urine. About two-thirds of the urinary C14 was present as one or more conjugates which could be split with β- glucuronidase. This hydrolysis produced several radioactive products, none of which was tripelennamine itself. The antihistaminic activity (intestinal strip method) of the conjugate and of the hydrolysis product was very small in comparison to tripelennamine.Less than 10% of the urinary C14 could be extracted with chloroform. Paper electrophoresis differentiated this extractable fraction from tripelennamine and its antihistaminic activity was found to be smaller than that of tripelennamine.Liver slices and minces metabolize tripelennamine in vitro. The solvent partition characteristics of the main metabolite formed resemble those of the main conjugated component of the urine.It seems likely that the major metabolic modification of tripelennamine consists of hydroxylation in one or more positions followed by conjugation, probably with glucuronic acid. Indications of changes at the dimethylamino group were also noted.Studies were also carried out with C14-tripelennamine methiodide. The distribution-excretion pattern of radioactivity obtained with the methiodide resembles that found with tripelennamine hydrochloride, but uptake by the lungs was less in the case of the quaternary salt. Solvent partition and chromatographic examination of the urines revealed two major radioactive fractions, one extractable with chloroform and one remaining in the aqueous residue. Neither component is tripelennamine or tripelennamine methiodide." @default.
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• W2277683163 date "1959-01-01" @default.
• W2277683163 modified "2023-09-23" @default.
• W2277683163 title "The distribution, excretion and metabolism of C14 labeled tripelennamine (pyribenzamine) by guinea pigs." @default.
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