Abstract

ENHANCING THE INTESTINAL ABSORPTION OF METFORMIN MOLECULE VIA HPEPT1 TRANSPORTERS

Najwan K. Jubair*

ABSTRACT

Type II diabetes mellitus (DM) is a chronic metabolic disorder with an increasing global prevalence and incidence. It is characterized by raised blood glucose levels as a result of insulin resistance and/ or pancreatic beta-cell failure. Metformin is a widely prescribed anti-hyperglycemic agent used for treatment of type II diabetes mellitus particularly in obese patients. Metformin accumulates in enterocytes during oral absorption with low bioavailability range between 40%-60%. Therefore, new metformin derivatives were synthesized by incorporation of metformin molecule to valine and arginine amino acids with their esters (A4-5) and (B 4-5) respectively via glycolic acid spacer. The chemical structure of the intermediates and the final compounds were confirmed by measuring their melting points, FT-IR spectroscopy and HNMR spectroscopy of the final compounds. Preliminary antidiabetic studies of the final compounds were evaluated by using streptozotocin induced diabetic rat model and it revealed significant anti-hyperglycemic activity of the final compounds compared to metformin.

Keywords: metformin; arginine; valine; intestinal peptide transporter hPepT1; antidiabetic evaluation.