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Disposition and metabolism of TAK-438 (vonoprazan fumarate), a novel potassium-competitive acid blocker, in rats and dogs. | LitMetric

Disposition and metabolism of TAK-438 (vonoprazan fumarate), a novel potassium-competitive acid blocker, in rats and dogs.

Xenobiotica

a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.

Published: March 2017

AI Article Synopsis

Article Abstract

1. Following oral administration of [C]TAK-438, the radioactivity was rapidly absorbed in rats and dogs. The apparent absorption of the radioactivity was high in both species. 2. After oral administration of [C]TAK-438 to rats, the radioactivity in most tissues reached the maximum at 1-hour post-dose. By 168-hour post-dose, the concentrations of the radioactivity were at very low levels in nearly all the tissues. In addition, TAK-438F was the major component in the stomach, whereas TAK-438F was the minor component in the plasma and other tissues. High accumulation of TAK-438F in the stomach was observed after oral and intravenous administration. 3. TAK-438F was a minor component in the plasma and excreta in both species. Its oxidative metabolite (M-I) and the glucuronide of a secondary metabolite formed by non-oxidative metabolism of M-I (M-II-G) were the major components in the rat and dog plasma, respectively. The glucuronide of M-I (M-I-G) and M-II-G were the major components in the rat bile and dog urine, respectively, and most components in feces were other unidentified metabolites. 4. The administered radioactive dose was almost completely recovered. The major route of excretion of the drug-derived radioactivity was via the feces in rats and urine in dogs.

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Source
http://dx.doi.org/10.1080/00498254.2016.1182667DOI Listing

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