| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Reports |
ORVILLE G. KOLTERMAN, M.D., is Senior Vice-President, Clinical Affairs; DENNIS D. KIM, M.D., is Senior Director, Medical Affairs; LARRY SHEN, PH.D., is Senior Director, Biometrics; JAMES A. RUGGLES, PH.D., is Associate Director Medical Writing, Medical Affairs; LORETTA L. NIELSEN, PH.D., is Senior Medical Writer, Medical Affairs; MARK S. FINEMAN, B.S., is Senior Director, Clinical Affairs; and ALAIN D. BARON, M.D., is Senior Vice-President Research, Amylin Pharmaceuticals Inc., San Diego, CA.
Address correspondence to Dr. Kolterman at Amylin Pharmaceuticals Inc., 9360 Towne Centre Drive, Suite 110, San Diego, CA 92121 (okolterman{at}amylin.com).
Methods. Two randomized, single-blind, placebo-controlled studies were conducted. Treatment with oral antidiabetic agents was stopped 14 days before study initiation. In the first study (study A), eight subjects received placebo, 0.1-, 0.2-, 0.3-, and either 0.4-µg/kg exenatide or placebo five minutes before a meal combined with liquid acetaminophen (to assess the rate of gastric emptying) on days 1, 3, 5, 7, and 9. In the second study (study B), subjects received a single s.c. dose of exenatide or placebo on consecutive days. Part 1 of study B used exenatide doses of 0.01 and 0.1 µg/ kg; 0.02-, 0.05-, and 0.1-µg/kg doses were given in part 2. After an overnight fast, the study drug was injected 15 minutes before a meal (part 1) and before a meal and acetaminophen (part 2). Parts 1 and 2 of study B enrolled six and eight patients, respectively.
Results. In both studies, plasma exenatide pharmacokinetic profiles appeared dose proportional. Exenatide doses of 0.02–0.2 µg/kg dose-dependently lowered postprandial glucose excursions. Exenatide suppressed postprandial plasma glucagon and slowed gastric emptying. There were no serious adverse events and no patient withdrawals related to treatment. Nausea and vomiting were the most common adverse events and were mild to moderate in severity at doses ranging from 0.02 to 0.2 µg/kg.
Conclusion. Administration of preprandial exenatide by s.c. injection resulted in dose-proportional exenatide pharmacokinetics and antidiabetic pharmacodynamic activity. At doses ranging from 0.02 to 0.2 µg/kg, exenatide dose-dependently reduced postprandial plasma glucose excursion by insulinotropism, suppression of plasma glucagon, and slowing of gastric emptying.
Index terms: Antidiabetic agents; Blood levels; Diabetes mellitus; Dosage; Drug administration routes; Exenatide; Gastric emptying; Mechanism of action; Pharmacodynamics; Pharmacokinetics; Toxicity
Purpose. The pharmacology and tolerability of exenatide in patients with type 2 diabetes mellitus were studied.
This article has been cited by other articles:
|
|
 |
|
  V. Ionut, D. Zheng, D. Stefanovski, and R. N. Bergman Exenatide can reduce glucose independent of islet hormones or gastric emptying Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E269 - E277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F Van Gaal, S. W Gutkin, and M. A Nauck Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control? Eur. J. Endocrinol., June 1, 2008; 158(6): 773 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Salehi, B. A. Aulinger, and D. A. D'Alessio Targeting {beta}-Cell Mass in Type 2 Diabetes: Promise and Limitations of New Drugs Based on Incretins Endocr. Rev., May 1, 2008; 29(3): 367 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Martin Beyond Glycemic Control: The Effects of Incretin Hormones in Type 2 Diabetes The Diabetes Educator, May 1, 2008; 34(Supplement_3): 66S - 72S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Bloom and M. F. Crutchlow New-Onset Diabetes Mellitus in the Kidney Recipient: Diagnosis and Management Strategies Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(Supplement_2): S38 - S48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Holst The Physiology of Glucagon-like Peptide 1 Physiol Rev, October 1, 2007; 87(4): 1409 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zinman, B. J. Hoogwerf, S. Duran Garcia, D. R. Milton, J. M. Giaconia, D. D. Kim, M. E. Trautmann, and R. G. Brodows The Effect of Adding Exenatide to a Thiazolidinedione in Suboptimally Controlled Type 2 Diabetes: A Randomized Trial Ann Intern Med, April 3, 2007; 146(7): 477 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Soon, P. A. Kothare, H. Linnebjerg, S. Park, E. Yuen, K. F. Mace, and S. D. Wise Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy asian men. J. Clin. Pharmacol., October 1, 2006; 46(10): 1179 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Yoo, D. M. Triller, and D. J. Yoo Exenatide: A New Option for the Treatment of Type 2 Diabetes Ann. Pharmacother., October 1, 2006; 40(10): 1777 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Odegard, S. M. Setter, and J. L. Iltz Update in the pharmacologic treatment of diabetes mellitus: focus on pramlintide and exenatide. The Diabetes Educator, September 1, 2006; 32(5): 693 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Fehse, M. Trautmann, J. J. Holst, A. E. Halseth, N. Nanayakkara, L. L. Nielsen, M. S. Fineman, D. D. Kim, and M. A. Nauck Exenatide Augments First- and Second-Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5991 - 5997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Gault, N. Irwin, B. D. Green, J. T. McCluskey, B. Greer, C. J. Bailey, P. Harriott, F. P.M. O'Harte, and P. R. Flatt Chemical Ablation of Gastric Inhibitory Polypeptide Receptor Action by Daily (Pro3)GIP Administration Improves Glucose Tolerance and Ameliorates Insulin Resistance and Abnormalities of Islet Structure in Obesity-Related Diabetes Diabetes, August 1, 2005; 54(8): 2436 - 2446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Gedulin, S. E. Nikoulina, P. A. Smith, G. Gedulin, L. L. Nielsen, A. D. Baron, D. G. Parkes, and A. A. Young Exenatide (Exendin-4) Improves Insulin Sensitivity and {beta}-Cell Mass in Insulin-Resistant Obese fa/fa Zucker Rats Independent of Glycemia and Body Weight Endocrinology, April 1, 2005; 146(4): 2069 - 2076. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
