Back to Search Start Over

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

Authors :
Kothare PA
Linnebjerg H
Isaka Y
Uenaka K
Yamamura A
Yeo KP
de la Peña A
Teng CH
Mace K
Fineman M
Shigeta H
Sakata Y
Irie S
Source :
Journal of clinical pharmacology [J Clin Pharmacol] 2008 Dec; Vol. 48 (12), pp. 1389-99.
Publication Year :
2008

Abstract

In this single-blind, parallel, placebo-controlled study, the pharmacokinetics, pharmacodynamics, tolerability, and safety of subcutaneous exenatide were evaluated in 40 Japanese patients with type 2 diabetes. Patients were allocated to 4 groups and randomized to receive exenatide (n = 8/group) or placebo (n = 2/group), with all receiving placebo on day 1. On day 2, patients received single-dose exenatide (2.5 microg [group A] or 5 microg [groups B, C, and D]) or placebo and then bid on days 3 to 5. On days 6 to 10, groups A and B continued on 2.5 and 5 microg bid; groups C and D received 10 and 15 microg bid, respectively. The last dose was given on the morning of day 10. All adverse events were mild or moderate in severity. Exenatide was generally well tolerated up to 10 microg. Exenatide was well absorbed with a median t(max) of 1.5 hours and mean t((1/2)) of 1.6 hours; exposure increased with dose. Up to 10 microg, exenatide reduced postprandial glucose concentrations in a dose-dependent fashion compared with placebo; decreases were similar for 10 and 15 microg. An E(max) model demonstrated that doses higher than 2.5 microg were necessary for adequate glycemic response. Based on tolerability and pharmacokinetic/pharmacodynamic relationships, 5 and 10 microg exenatide may be considered for further clinical development in Japanese patients with type 2 diabetes.

Details

Language :
English
ISSN :
0091-2700
Volume :
48
Issue :
12
Database :
MEDLINE
Journal :
Journal of clinical pharmacology
Publication Type :
Academic Journal
Accession number :
19047364
Full Text :
https://doi.org/10.1177/0091270008323750