| Primary information |
|---|
| ID | 1478 |
| ThPP ID | Th1098 |
| Therapeutic Peptide/Protein Name | Exenatide |
| Sequence | HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 4186.6 |
| Chemical Formula | C184H282N50O60S |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Mean terminal half-life is 2.4 hours. |
| Description | Derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern United States. It is a functional analog of Glucagon-Like Peptide-1 (GLP-1) peptide. |
| Indication/Disease | Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control. |
| Pharmacodynamics | Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins. |
| Mechanism of Action | Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals. |
| Toxicity | Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations. |
| Metabolism | N.A. |
| Absorption | Following subcutaneous administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2.1 hours. |
| Volume of Distribution | 28.3 L |
| Clearance | Apparent cl=9.1 L/hr |
| Categories | Hypoglycemic Agents |
| Patents Number | US6872700 |
| Date of Issue | 15/01/04 |
| Date of Expiry | 15/01/24 |
| Drug Interaction | N.A. |
| Target | Glucagon-like peptide 1 receptor |
| Information of corresponding available drug in the market |
|---|
| Brand Name | BYETTA |
| Company | N.A. |
| Brand Discription | BYETTA (exenatide) is a synthetic peptide that was originally identified in the lizard Heloderma suspectum. Exenatide differs in chemical structure and pharmacological action from insulin, sulfonylureas (including D-phenylalanine derivatives and meglitinides), biguanides, thiazolidinediones, alpha-glucosidase inhibitors, amylinomimetics and dipeptidyl peptidase-4 inhibitors.Exenatide is a 39-amino acid peptide amide. Exenatide has the empirical formula C184H282N50O60S and molecular weight of 4186.6 Daltons. The amino acid sequence for exenatide is shown below.H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu -Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 |
| Prescribed for | BYETTA (exenatide injection) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. |
| Chemical Name | N.A. |
| Formulation | BYETTA (exenatide injection) is supplied for SC injection as a sterile, preserved isotonic solution in a glass cartridge that has been assembled in a pen-injector (pen). Each milliliter (mL) contains 250 micrograms (mcg) synthetic exenatide, 2.2 mg metacresol as an antimicrobial preservative, mannitol as a tonicity-adjusting agent, and glacial acetic acid and sodium acetate trihydrate in water for injection as a buffering solution at pH 4.5. Two prefilled pens are available to deliver unit doses of 5 mcg or 10 mcg. Each prefilled pen will deliver 60 doses to provide for 30 days of twice daily administration (BID). |
| Physcial Appearance | N.A. |
| Route of Administration | N.A. |
| Recommended Dosage | BYETTA (exenatide injection) should be initiated at 5 mcg administered twice daily at any time within the 60-minute period before the morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart). BYETTA (exenatide injection) should not be administered after a meal. Based on clinical response, the dose of BYETTA (exenatide injection) can be increased to 10 mcg twice daily after 1 month of therapy. Initiation with 5 mcg reduces the incidence and severity of gastrointestinal side effects. Use BYETTA (exenatide injection) only if it is clear, colorless and contains no particles. |
| Contraindication | BYETTA (exenatide injection) is not a substitute for insulin. BYETTA (exenatide injection) should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. The concurrent use of BYETTA (exenatide injection) with insulin has not been studied and cannot be recommended.Based on postmarketing data BYETTA (exenatide injection) has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. BYETTA (exenatide injection) has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYETTA (exenatide injection) . Other antidiabetic therapies should be considered in patients with a history of pancreatitis. |
| Side Effects | Severe allergic reactions include severe rash or itching, swelling of your face, lips, and throat that may cause difficulty breathing or swallowing, feeling faint or dizzy and very rapid heartbeat. Inflammation of the pancreas (pancreatitis) may happen, which may be severe and lead to death. Your risk for getting low blood sugar (hypoglycemia) is higher. Signs and symptoms of low blood sugar may include headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, and feeling jittery. |
| Useful Link | N.A. |
| PubMed ID | 25645567, 25616979, 25594949, 25589020, 17619527, 16230722 |
| 3-D Structure | Th1098 (View) or (Download) |
| Primary information |
|---|
| ID | 1479 |
| ThPP ID | Th1098 |
| Therapeutic Peptide/Protein Name | Exenatide |
| Sequence | HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 4186.6 |
| Chemical Formula | C184H282N50O60S |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Mean terminal half-life is 2.4 hours. |
| Description | Derived from a compound found in the saliva of the Gila monster, a large lizard native to the southwestern United States. It is a functional analog of Glucagon-Like Peptide-1 (GLP-1) peptide. |
| Indication/Disease | Indicated as adjunctive therapy to improve glycemic control in patients with Type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of both, but have not achieved adequate glycemic control. |
| Pharmacodynamics | Exenatide is an incretin mimetic, which has glucoregulatory effects. While it is has blood-sugar lowering actions alone, it can also be combined with other medications such as pioglitazone, metformin, sulfonylureas, and/or insulin to improve glucose control. The approved use of exenatide is with either sulfonylureas, metformin and thiazolinediones. The medication is injected twice per day using a pre-filled pen device. Typical human responses to exenatide plus eating include improvements in the initial rapid release of endogenous insulin, suppression of glucagon release by the pancreas, regulation of gastric empyting and reduced appetite; all behaviors more typical of individuals without blood sugar control problems. Exenatide is self-regulating in that in lowers blood sugar when levels are elevated but does not continue to lower blood sugar when levels return to normal, unlike with sulfonylureas or insulins. |
| Mechanism of Action | Exenatide is a functional analog of the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals. |
| Toxicity | Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations. |
| Metabolism | N.A. |
| Absorption | Following subcutaneous administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2.1 hours. |
| Volume of Distribution | 28.3 L |
| Clearance | Apparent cl=9.1 L/hr |
| Categories | Hypoglycemic Agents |
| Patents Number | US5424286 |
| Date of Issue | 02/12/00 |
| Date of Expiry | 02/12/20 |
| Drug Interaction | N.A. |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | BYDUREON |
| Company | Amylin Pharmaceuticals |
| Brand Discription | BYDUREON (exenatide extended-release for injectable suspension) is supplied as a sterile powder to be suspended in diluent and administered by subcutaneous injection. Exenatide is a 39-amino acid synthetic peptide amide with an empirical formula of C184H282N50O60S and a molecular weight of 4186.6 Daltons. The amino acid sequence for exenatide is shown below. H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-ValArg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 |
| Prescribed for | BYDUREON is an extended-release formulation of exenatide, administered as an injection once every 7 days (weekly). BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus |
| Chemical Name | N.A. |
| Formulation | Exenatide is incorporated in an extended-release microsphere formulation containing the 50:50 poly(D,L-lactide-co-glycolide) polymer (37.2 mg per dose) along with sucrose (0.8 mg per dose). The powder must be suspended in the diluent prior to injection. The diluent for the BYDUREON vial is supplied in a prefilled syringe within each single-dose tray. The diluent for the BYDUREON Pen is contained within each single-dose pen. Each configuration contains sufficient diluent to deliver 0.65 mL. The diluent is a clear, colorless to pale-yellow solution composed of carboxymethylcellulose sodium (19 mg), polysorbate 20 (0.63 mg), sodium phosphate monobasic monohydrate (0.61 mg), sodium phosphate dibasic heptahydrate (0.51 mg), sodium chloride (4.1 mg), and water for injection. Sodium hydroxide may be added during manufacture of BYDUREON Pen for pH adjustment. |
| Physcial Appearance | White to off-white powder that is available in a dosage strength of 2 mg exenatide per vial or per pen |
| Route of Administration | N.A. |
| Recommended Dosage | BYDUREON (2 mg per dose) should be administered once every 7 days (weekly). The dose can be administered at any time of day, with or without meals. |
| Contraindication | BYDUREON is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise. BYDUREON is not a substitute for insulin. BYDUREON should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. BYDUREON and BYETTA (exenatide) injection both contain the same active ingredient, exenatide, and therefore should not be used together. BYDUREON has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON. Other antidiabetic therapies should be considered in patients with a history of pancreatitis. |
| Side Effects | Possible thyroid tumors, including cancer, Allergic reaction Pancreatitis, Hypoglycemia |
| Useful Link | https://www.bydureon.com |
| PubMed ID | 25645567, 25616979, 25594949, 25589020, 17619527, 16230722 |
| 3-D Structure | Th1098 (View) or (Download) |