Indication: Fro the treatment of type II diabetes (combination therapy when administered with metformin)
Pharmacology: Not Available
Mechanism Of Action: Nateglinide is an amino-acid derivative that lowers blood glucose levels by stimulating insulin secretion from the pancreas. This action is dependent upon functioning beta-cells in the pancreatic islets. Nateglinide interacts with the ATP-sensitive potassium (K+ ATP ) channel on pancreatic beta-cells. The subsequent depolarization of the beta cell opens the calcium channel, producing calcium influx and insulin secretion. The extent of insulin release is glucose dependent and diminishes at low glucose levels. Nateglinide is highly tissue selective with low affinity for heart and skeletal muscle.
Drug Category: Hypoglycemic Agents; Meglitinides; ATC:A10BX03
Absorption: Rapidly absorbed in GI tract before a meal.
Interactions:
DrugBank: Interactions for Nateglinide
Interactions for Nateglinide:
In vitro drug metabolism studies indicate that Starlix is predominantly metabolized by the cytochrome P450
isozyme CYP2C9 (70%) and to a lesser extent CYP3A4 (30%). Starlix is a potential inhibitor of the CYP2C9 isoenzyme
in vivo as indicated by its ability to inhibit the in vitro metabolism of tolbutamide. Inhibition of
CYP3A4 metabolic reactions was not detected in in vitro experiments.
Glyburide: In a randomized, multiple-dose crossover study, patients with Type 2 diabetes
were administered 120 mg Starlix three times a day before meals for 1 day in combination with glyburide 10 mg daily.
There were no clinically relevant alterations in the pharmacokinetics of either agent.
Metformin: When Starlix 120 mg three times daily before meals was administered in
combination with metformin 500 mg three times daily to patients with Type 2 diabetes, there were no clinically
relevant changes in the pharmacokinetics of either agent.
Digoxin: When Starlix 120 mg before meals was administered in combination with a single
1-mg dose of digoxin to healthy volunteers, there were no clinically relevant changes in the pharmacokinetics of
either agent.
Warfarin: When healthy subjects were administered Starlix 120 mg three times daily
before meals for four days in combination with a single dose of warfarin 30 mg on day 2, there were no alterations in
the pharmacokinetics of either agent. Prothrombin time was not affected.
Diclofenac: Administration of morning and lunch doses of Starlix 120 mg in combination
with a single 75-mg dose of diclofenac in healthy volunteers resulted in no significant changes to the
pharmacokinetics of either agent.
Nateglinide is highly bound to plasma proteins (98%), mainly albumin. In vitro displacement studies with
highly protein-bound drugs such as furosemide, propranolol, captopril, nicardipine, pravastatin, glyburide, warfarin,
phenytoin, acetylsalicylic acid, tolbutamide, and metformin showed no influence on the extent of nateglinide protein
binding. Similarly, nateglinide had no influence on the serum protein binding of propranolol, glyburide, nicardipine,
warfarin, phenytoin, acetylsalicylic acid, and tolbutamide in vitro . However, prudent evaluation of
individual cases is warranted in the clinical setting.
Certain drugs, including nonsteroidal anti-inflammatory agents (NSAIDs), salicylates, monoamine oxidase
inhibitors, and non-selective beta-adrenergic-blocking agents may potentiate the hypoglycemic action of Starlix and
other oral antidiabetic drugs.
Certain drugs including thiazides, corticosteroids, thyroid products, and sympathomimetics may reduce the
hypoglycemic action of Starlix and other oral antidiabetic drugs.
When these drugs are administered to or withdrawn from patients receiving Starlix, the patient should be observed
closely for changes in glycemic control.
Chemical IUPAC Name: 2-[4-(1-methylethyl)cyclohexyl]carbonylamino-3-phenyl-propanoicacid
