Натеглинид

Описание

Nateglinide is a N-acylated D-phenylalanine marketed in Japan as novel orally active insulinotropic agent for the treatment of type-2 diabetes mellitus. It belongs to the class of nonsulfonylureas and shows some structural similarity to repaglinide, the only other representative in this family. In single pancreatic beta-cells isolated from rats, Nateglinide was found to specifically block the ATP-sensitive K+ channel resulting in an increase in intracellular calcium concentration. This primary action would underlie the mechanism by which Nateglinide markedly stimulates or potentiates, depending on glucose concentrations, insulin secretion from pancreatic beta-cells. Clinical studies demonstrated a good safety profile with a low potential for hypoglycemia. The pharmacokinetic profile was consistent with the changes of the blood glucose and plasma insulin level. Interestingly, Nateglinide exerts a rapid onset and short duration of action due to a rapid absorption and clearance. Unlike other similar agents, Nateglinide suppresses postprandial glucose elevations.

Химические свойства

Cyrstalline Solid

Определение

ChEBI: An N-acyl-D-phenylalanine resulting from the formal condensation of the amino group of D-phenylalanine with the carboxy group of trans-4-isopropylcyclohexanecarboxylic acid. An orally-ad inistered, rapidly-absorbed, short-acting insulinotropic agent, it is used for the treatment of type 2 diabetes mellitus.

Общее описание

Although nateglinide, N-(4-isopropylcyclohexanecarbonyl)-D-phenylalanine (Starlix), belongs tothe metaglinides, it is a phenylalanine derivative and representsa novel drug in the management of type 2 diabetes.

Механизм действия

Approved in the United States in late 2000, nateglinide is a rapidly absorbed insulin secretagogue that has a mechanism of action similar to that of repaglinide, with effects appearing within 20 minutes following oral dosing. Bioavailability is 73%, and it is 98% protein bound, primarily to albumin. Nateglinide is tissue selective, with low affinity for cardiac and skeletal muscle.

Метаболизм

It is metabolized in the liver, with 16% excreted in the urine unchanged. The major metabolites are hydroxyl derivatives (CYP2C9, 70%; CYP3A4, 30%) that are further conjugated to the glucuronide derivatives.