Thienopyridine P2Y12 receptor antagonists:unknown pharmacological active metabolites and metabolic activation mechanisms

Hagihara Katsunobu, Kazui Miho, Kurihara Atsushi, Ando Osamu, Izumi Takashi, Ikeda Toshihiko

doi:10.2745/dds.30.454

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チエノピリジン系P2Y12受容体阻害剤：長らく不明だった薬理活性体と活性化メカニズム
チエノピリジンケイ P2Y12 ジュヨウタイソガイザイ : ナガラクフメイダッタヤクリカッセイタイトカッセイカメカニズム

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As sulfa drug was found as the urinary metabolite of Prontosil in past times, early prodrugs were often discovered by chance. The prodrugs later on, however, have been synthesized by chemically modifying the pharmacologically active substance, most frequently, with an intension of increased lipophilicity for an improved intestinal absorption and efficient enzymatic conversion to the active substance in the body. This could be achieved based on plenty of knowledge on the activating enzymes like esterases. In cases where the chemical structures of active metabolites or the mechanisms of metabolic activation are unknown, however, we cannot implement such strategies. The examples are the thienopyridine antiplatelet agents whose active metabolites have not been structurally clarified for long even though their clinical usefulness as the anti-platelet drugs has been well established in human studies. In this article, we describe the mechanisms for metabolic activation of thienopyridines and impact of the differenes in the activation mechanism on the clinical outcomes.

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Drug Delivery System

Drug Delivery System 30 (5), 454-464, 2015

THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

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