Vildagliptin

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Vildagliptin, better known as Galvus

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Better Known as: Galvus

  • Marketed by: Novartis
  • Major Indication: Hyperglycemia & Type II Diabetes
  • Drug Class: Dipeptidyl Peptidase-4 (DPP-4) Inhibitor
  • Date of EMA Approval: 2008
  • 2009 Sales: N/A
  • Importance: Part of a new generation of DPP-4 Inhibitors. Was not approved by the FDA due to concerns over kidney impairment associated with the drug. It was however approved by the European Medicines Agency for use within the EU. Increasing evidence exists that all DPP-4 inhibitors can to certain malignant cancers.[1]
  • See Pharmaceutical Drugs for more information about other drugs and diseases.

Mechanism of Action

Dipeptidyl Peptidase-4 (DPP-4) is an antigenic membrane serine exopeptidase that cleaves proline dipeptides form the N-terminal end of protein substrates. DPP-4 plays a major role in glucose metabolism as it is responsible for the degradation of incretins, most notably Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIp). Incretins are a group of gastrointestinal hormones that stimulate insulin biosynthesis and inhibit glucagon secretion after consuming high glucose meals. Since Diabetes is typically caused by a deficiency in insulin secretion or by increased hepatic glucose production, preventing incretin degradation is a viable treatment for diabetics. Vildagliptin is a competitive inhibitor of DPP-4. By inhibiting DPP-4 and subsequently preventing the enzymatic degradation of GLP-1 and GIP, these incretins are able to potentiate the secretion of insulin and suppress the release of glucagon by the pancreas, resulting in controlled blood-glucose levels.[2] Although no crystal structure of Vildagliptin bound DPP-4 has been solved, it is believed to bind in a similar fashion to Sitagliptin and Saxagliptin.

Pharmacokinetics

DPP4 Inhibitor Pharmacokinetics
Parameter Vildagliptin
(Galvus) 		Sitagliptin
(Januvia) 		Saxagliptin
(Onglyza)
Tmax (hr) 1.75 1-4 2
Cmax (ng/ml) 290 330 34
Bioavailability (%) 85 87 67
Protein Binding (%) 9 38 0
T1/2 (hr) 2-3 12.4 2.5
AUC (ng/ml/hr) 1610 3470 101
IC50 (nM) 3 18 50
Renal Clearance (L/h) 13.0 21.0 13.8
Volume Distribution (L) 71 198 151
Dosage (mg) 100 100 5
Metabolism Hydrolysis Hepatic (CYP3A4 & CYP2C8) Hepatic (CYP3A4)

For Pharmacokinetic Data References, see: References

References

  1. ↑ Wesley UV, McGroarty M, Homoyouni A. Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res. 2005 Feb 15;65(4):1325-34. PMID:15735018 doi:10.1158/0008-5472.CAN-04-1852
  2. ↑ Barnett A. DPP-4 inhibitors and their potential role in the management of type 2 diabetes. Int J Clin Pract. 2006 Nov;60(11):1454-70. PMID:17073841 doi:10.1111/j.1742-1241.2006.01178.x


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