Fliptin Mechanism of Action

Pharmacology: Sitagliptin is a DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.
Pharmacokinetics: FLIPTIN film-coated tablet has been studied in an open-label, randomized, single dose, two-period, two-sequence, cross-over study under fasting conditions which included 24 healthy adult male and female subjects (age between 18-55 years). The AUC_0-t and C_max of sitagliptin were defined as the main parameters in order to assess possible bioequivalence between the test drug and the comparator drug. The bioequivalence of the two products was concluded based on the 90% confidence intervals of the test/comparator geometric mean ratios of sitagliptin's AUC_0-t and C_max which were within the range of 80.00-125.00%.
Following oral administration of 100 mg FLIPTIN film-coated tablet, the mean of AUC_0-t and AUC_0-inf sitagliptin were 4,001.27 ng.hour/ml and 4,207.15 ng.hour/ml, respectively. The mean of maximum plasma concentration (C_max) of sitagliptin was 470.90 ng/ml with the median (range) of t_max was 2.00 (0.50-5.00) hours. The mean elimination half-life (t_½) of sitagliptin was 7.88 hours. The geometric mean ratios (90% confidence intervals) of sitagliptin were 100.30% (94.64%-106.29%) for AUC_0-t and 102.66% (95.63%-110.22%) for C_max.
The result of the study showed that the pharmacokinetic parameters of FLIPTIN film-coated tablet were within the acceptance range for bioequivalence, therefore, FLIPTIN film-coated tablet were similar or bioequivalent to the comparator drug.