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• W2058552757 abstract "The absorption process in animals of TAK-491, designed as ester-based prodrug with medoxomil moiety, was evaluated. In the plasma of rats and dogs, TAK-536, the pharmacologically active metabolite, was present as the main component with hardly detectable concentrations of TAK-491 after oral administration of TAK-491. In the rat portal plasma, TAK-536 was also present as the main component with hardly detectable concentrations of TAK-491 after jejunal loop injection of TAK-491, suggesting TAK-491 was absorbed from small intestine and hydrolyzed almost completely during absorption.Caco-2 study indicated the permeability of TAK-491 was improved by prodrug modification and the compound could be mainly transferred as TAK-491. This is well consistent with the facts that the AUC and Tmax of TAK-536 after oral administration of TAK-491 were higher and shorter than those after oral administration of TAK-536 in dogsHydrolysis of TAK-491 is observed not only by the intestinal and hepatic S9 fraction, but also by plasma and human serum albumin. However, medoxomil alcohol wasn’t detected during the hydrolysis of TAK-491. These metabolic features of TAK-491 were similar to olmesartan medoxomil, suggesting the hydrolytic pathway and enzymes for TAK-491 when catalyzing to TAK-536 would be the same as olmesartan medoxomil." @default.
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• W2058552757 date "2012-08-07" @default.
• W2058552757 modified "2023-09-27" @default.
• W2058552757 title "Absorption of TAK-491, a new angiotensin II receptor antagonist, in animals" @default.
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• W2058552757 doi "https://doi.org/10.3109/00498254.2012.708797" @default.
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