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Merck
  • The first bioreversible prodrug of metformin with improved lipophilicity and enhanced intestinal absorption.

The first bioreversible prodrug of metformin with improved lipophilicity and enhanced intestinal absorption.

Journal of medicinal chemistry (2009-06-16)
Kristiina M Huttunen, Anne Mannila, Krista Laine, Eeva Kemppainen, Jukka Leppänen, Jouko Vepsäläinen, Tomi Järvinen, Jarkko Rautio
要旨

Metformin is a potent antidiabetic agent and currently used as a first-line treatment for patients with type 2 diabetes. Unfortunately, the moderate absorption and uncomfortable gastrointestinal adverse effects associated with metformin therapy impair its use. In this study, two novel prodrugs of a biguanidine functionality containing antidiabetic agent, metformin, were designed, synthesized, and evaluated in vitro and in vivo to accomplish improved lipophilicity and, consequently, enhanced oral absorption of this highly water-soluble drug. These results represent that the more lipophilic prodrug 2a biotransformed quantitatively to metformin mainly after absorption. The enhanced oral absorption consequently promoted the bioavailability of metformin from 43% to 65% in rats. Thus, this novel prodrug may offer a solution to reduce the required daily doses of metformin, which may decrease the uncomfortable adverse effects associated with metformin therapy.

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Sigma-Aldrich
スルファメラジン, ReagentPlus®, ≥99.0%
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Supelco
スルファメラジン, VETRANAL®, analytical standard
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