| Indication | For treatment of NIDDM in conjunction with diet and exercise. |
| Pharmacodynamics | Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Chlorpropamide is twice as potent as the related second-generation agent glipizide. |
| Mechanism of action | Sulfonylureas such as chlorpropamide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. |
| Absorption | Readily absorbed from the GI tract. Peak plasma concentrations occur within 2-4 hours and the onset of action occurs within one hour. The maximal effect of chlorpropamide is seen 3-6 hours following oral administration. |
| Volume of distribution | Not Available |
| Protein binding | Highly bound to plasma proteins. |
| Metabolism | Up to 80% of dose is metabolized likely through the liver to to 2-hydroxylchlorpropamide (2-OH CPA), p-chlorobenzenesulfonylurea (CBSU), 3-hydroxylchlorpropamide (3-OH CPA), and p-chlorobenzenesulfonamide (CBSA); CBSA may be produced by decomposition in urine. It is unknown whether chlorpropamide metabolites exert hypoglycemic effects. |
| Route of elimination | 80-90% of a single oral dose is excreted in the urine as unchaged drug and metabolites within 96 hours. |
| Half life | Approximately 36 hours with interindividual variation ranging from 25-60 hours. Duration of effect persists for at least 24 hours. |
| Clearance | Not Available |
| Toxicity | IPN-RAT LD50 580 mg/kg |