Saxagliptin

Absorption

Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng?h/mL and 214 ng?h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. Saxagliptin did not accumulate following repeated doses. The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Bioavailability, 2.5 - 50 mg dose = 67%

Toxicity

Adverse reactions reported in ≥5% of patients treated with saxagliptin and more commonly than in patients treated with placebo are: upper respiratory tract infection, urinary tract infection, and headache.

The Uses of Saxagliptin

Saxagliptin is a potent and selective reversible inhibitor of dipeptidyl peptidase-4, which is being developed for the treatment of type 2 diabetes. It is absorbed rapidly after oral administration an d has a pharmacokinetic profile compatible with once daily dosing.

Background

Saxagliptin (rINN) is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. FDA approved on July 31, 2009.

Indications

Treatment of type 2 diabetes mellitus to improve glycemic control in combination with other agents or as monotherapy.

What are the applications of Application

Saxagliptin is a potent and selective reversible inhibitor of dipeptidyl peptidase-4

Pharmacokinetics

Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong the QTc interval to a clinically significant degree.

Metabolism

The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). 50% of the absorbed dose will undergo hepatic metabolism. The major metabolite of saxagliptin, 5-hydroxy saxagliptin, is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.