Nateglinide [N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine] is a novel, highly physiologic, glucose regulator recently approved for the treatment of type-2 diabetes mellitus. Nateglinide has a rapid onset and short duration of insulinotropic action that results in reduction of glucose level. Nateglinide block the K-ion channels in pancreatic beta-cells, facilitating insulin secretion.
In the present investigation formulation and evaluation of nateglinide mucoadhesive microspheres, the basic idea behind the development of such a system is to maintain a constant level of drug in blood plasma. The microspheres containing nateglinide drug in the gastric fluid and slowly dissolves at a predetermined …show more content…
Somatostatin analogues may potentiate or attenuate the hypoglycemic action of nateglinide.When these drugs are administered to or withdrawn from patients receiving nateglinide , the patient should be observed closely for changes in glycemic control.
The pharmacokinetics of nateglinide were not affected by the composition of a meal (high protein, fat, or carbohydrate). However, peak plasma levels were significantly reduced when Starlix was administered 10 minutes prior to a liquid meal. Nateglinide did not have any effect on gastric emptying in healthy subjects as assessed by acetaminophen testing.
3.6 MECHANISM OF ACTION
Nateglinide drug is fixing on specific receptors and acts through the potassium channel from the pancreatic and the extra-pancreatic level. At pancreatic level, increase insulin secretion and at the level of pancreatic beta cells, they increase the number of insulin receptors. At extra-pancreatic s nateglinide decreases hepatic gluconeogenesis (glucose synthesis from non-carbohydrate sources), increased glycolysis and enhances insulin action in skeletal muscle and in adipose …show more content…
Type 2 diabetes mellitus is increasing to near epidemic proportions, with a reported 190 million patients worldwide. Use of oral antidiabetic medications is increasing along with a proportional increase in adverse events. Oral antidiabetic medications can be separated by mechanism of action into two groups: hypoglycemics (sulfonylureas and meglitinides) and antihyperglycemics (biguanides and alpha-glucosidase inhibitors). The hypoglycemic agents pose a significant risk of morbidity, mortality, and permanent sequelae secondary to prolonged periods of hypoglycemia. However, outcomes are routinely good if intervention is initiated early, with the primary goal return of euglycemia using supplemental dextrose infusion and octreotide to reduce further insulin secretion. Metformin-associated lactic acidosis (MALA) can occur with both acute and chronic metformin exposure. While MALA is not common, its associated rates of morbidity and mortality can be high. Secondary to MALA, the patient may experience changes in the central nervous system, cardiovascular collapse, renal failure, and death. The primary goals of therapy are restoration of acid-base status and removal of metformin, using hemodialysis and bicarbonate therapy. There is no specific antidote for MALA. The alpha-glucosidase inhibitors and thiazolidinediones pose minimal risk of adverse events in acute overdose.