Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus

American Journal of Health-System Pharmacy

Volumn 62, Issue 2, 2005, Pages 173-181

  Kolterman, Orville G ^a   Kim, Dennis D ^a   Shen, Larry ^a   Ruggles, James A ^a   Nielsen, Loretta L ^a   Fineman, Mark S ^a   Baron, Alain D ^a  

^a AMYLIN PHARMACEUTICALS INC   (United States)

Author keywords

Antidiabetic agents; Blood levels; Diabetes mellitus; Dosage; Drug administration routes; Exenatide; Gastric emptying; Mechanism of action; Pharmacodynamics; Pharmacokinetics; Toxicity

Indexed keywords

ANTIDIABETIC AGENT; EXENDIN 4; PARACETAMOL; PLACEBO;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIARRHEA; DIET RESTRICTION; DOSE RESPONSE; DRUG ABSORPTION; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; GLUCAGON BLOOD LEVEL; GLUCOSE BLOOD LEVEL; HEADACHE; HUMAN; HYPOGLYCEMIA; MALE; NAUSEA AND VOMITING; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; STOMACH EMPTYING; TREATMENT OUTCOME;

EID: 15444367142     PISSN: 10792082     EISSN: None     Source Type: Journal    
DOI: 10.1093/ajhp/62.2.173     Document Type: Article

References (35)

1. United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 1998; 352:837-53.
2. United Kingdom Prospective Diabetes Study Group. Overview of 6 years' therapy of type 2 diabetes: a progressive disease. Diabetes. 1995; 44:1249-58.
3. American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study (position statement). Diabetes Care. 2002; 25(suppl 1):S28-32.
4. Harris MI, Eastman RC, Cowie CC et al. Racial and ethnic differences in glycemic control of adults with type 2 diabetes. Diabetes Care. 1999; 22:403-8
5. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA. 2002; 287:360-72.
6. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999; 131:281-303.
7. Eng J, Kleinman WA, Singh L et al. Isolation and characterization of exendin-4, an exendin-3 analogue from Heloderma suspectum venom. J Biol Chem. 1992; 267:7402-5.
8. Young A. Glucagon-like peptide-1, exendin and insulin sensitivity. In: Hansen B, Shafrir E, eds. Insulin resistance and insulin resistance syndrome. New York: Harwood Academic Press; 2002:235-62.
9. Chen YE, Drucker D. Tissue-specific expression of unique mRNAs that encode pro-glucagon-derived peptides or exendin-4 in the lizard. J Biol Chem. 1997; 272:4108-15
10. Young AA, Gedulin BR, Bhavsar S et al. Glucose-lowering and insulin-sensitizing actions of exendin-4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes. 1999; 48:1026-34.
11. Egan JM, Clocquet AR, Elahi D. The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. J Clin Endocrinol Metab. 2002; 87:1282-90.
12. Parkes DG, Pittner R, Jodka C et al. Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro. Metabolism. 2001; 50:583-9.
13. Szayna M, Doyle ME, Betkey JA et al. Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology. 2000; 141:1936-41.
14. Nielsen LL, Baron AD. Pharmacology of exenatide (synthetic exendin-4) for the treatment of type 2 diabetes. Curr Opin Investig Drugs. 2003; 4:401-5.
15. Xu G, Stoffers DA, Habener JF et al. Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes. 1999; 48:2270-6.
16. Tourrel C, Bailbé D, Lacorne M et al. Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the β-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4. Diabetes. 2002; 51:1443-52.
17. Tourrel C, Bailbé D, Meile MJ et al. Glucagon-like peptide-1 and exendin-4 stimulate β-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes. 2001; 50:1562-70.
18. Rayner CK, Samsom M, Jones KL et al. Relationships of upper gastrointestinal motor and sensory function with glycemic mie control. Diabetes Care. 2001; 24:371-81.
19. Greig NH, Holloway HW, De Ore KA et al. Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia. 1999; 42:45-50.
20. Goke R, Fehmann HC, Linn T et al. Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells. J Biol Chem. 1993; 268: 19650-5.
21. World Medical Association declaration of Helsinski. Recommendations guiding physicians in biomedical research involving human subjects. JAMA. 1997; 277:925-6.
22. Clements JA, Heading RC, Nimmo WS et al. Kinetics of acetaminophen absorption and gastric emptying in man. Clin Pharmacol Ther. 1978; 24:420-31.
23. Fineman MS, Bicsak TA, Shen LZ et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care. 2003; 26:2370-7.
24. Mallinckrodt CH, Clark SW, Carroll RJ et al. Assessing response profiles from incomplete longitudinal clinical trial data under regulatory considerations. J Biopharm Stat. 2003; 13:179-90.
25. Parkes D, Jodka C, Smith P et al. Pharmacokinetic actions of exendin-4 in the rat: comparison with glucagon-like peptide-1. Drug Dev Res. 2001; 53:260-7.
26. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology. 1995; 136:3585-96.
27. Deacon CF, Nauck MA, Toft-Nielsen M et al. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type 2 diabetic patients and in healthy subjects. Diabetes. 1995; 44:1126-31.
28. Kolterman OG, Buse JB, Fineman MS et al. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003; 88:3082-9.
29. Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes. 2000; 49:1751-60.
30. Mahler RJ, Adler ML. Type 2 diabetes mellitus: update on diagnosis, pathophysiology, and treatment. J Clin Endocrinol Metab. 1999; 84:1165-71.
31. Moore MC, Cherrington AD. Regulation of net hepatic glucose uptake: interaction of neural and pancreatic mechanisms. Reprod Nutr Dev. 1996; 36:399-406.
32. Moyses C, Young A, Kolterman O. Modulation of gastric emptying as a therapeutic approach to glycaemic control. Diabet Med. 1996; 13(9, suppl 5):S34-8.
33. Green GM, Guan D, Schwartz JG et al. Accelerated gastric emptying of glucose in Zucker type 2 diabetic rats: role in postprandial hyperglycaemia. Diabetologia. 1997; 40:136-42.
34. Harju E, Nordback I. Postprandial hyperglycemia after different carbohydrates in patients with total gastrectomy. Surg Gynecol Obstet. 1987; 165:41-5.
35. MacGregor IL, Gueller R, Watts HD et al. The effect of acute hyperglycemia on gastric emptying in man. Gastroenterology. 1976; 70:190-6.