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Drug Res (Stuttg) 2014; 64(3): 130-135
DOI: 10.1055/s-0033-1353185
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Relationship between Anagliptin Concentration Showing Over 80% Inhibition of Plasma Dipeptidyl Peptidase-4 Activity and its Protective Effect against Glucagon-like Peptide-1 Degradation

S. Furuta
1   Sanwa Kagaku Kenkyusho, Co. Ltd, Pharmaceutical Research Laboratories, Mie, Japan
,
M. Goto
1   Sanwa Kagaku Kenkyusho, Co. Ltd, Pharmaceutical Research Laboratories, Mie, Japan
,
M. Tamura
1   Sanwa Kagaku Kenkyusho, Co. Ltd, Pharmaceutical Research Laboratories, Mie, Japan
,
S. Yamashita
1   Sanwa Kagaku Kenkyusho, Co. Ltd, Pharmaceutical Research Laboratories, Mie, Japan
,
K. Nakaya
1   Sanwa Kagaku Kenkyusho, Co. Ltd, Pharmaceutical Research Laboratories, Mie, Japan
,
Y. Furuta
1   Sanwa Kagaku Kenkyusho, Co. Ltd, Pharmaceutical Research Laboratories, Mie, Japan
› Author Affiliations
Further Information

Publication History

received 03 July 2013

accepted 27 July 2013

Publication Date:
21 August 2013 (online)

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The Relationship between Anagliptin Concentration Showing Over 80% Inhibition of Plasma Dipeptidyl Peptidase-4 Activity and its Protective Effect against Glucagon-like Peptide-1 DegradationDrug Res (Stuttg) 2014; 64(08): 448-448
DOI: 10.1055/s-0034-1375636

Abstract

In dipeptidyl peptidase-4 (DPP-4) inhibitors, the inhibition of plasma DPP-4 activity by 80% is considered sufficient to have an effect on glycemic control improvement through the elevation of intact glucagon-like peptide-1 (GLP-1). To clarify whether or not the 80% inhibition is sufficient to protect against GLP-1 degradation, we investigated rats with a continuous infusion of exogenous GLP-1. When GLP-1 was infused into the femoral or portal vein, the steady state active GLP-1 levels in plasma significantly increased (P<0.05) at the 80% inhibitory concentration (IC80) of anagliptin (a highly selective DPP-4 inhibitor) against plasma DPP-4 activity, compared with control. In addition, the peptide levels increased in a concentration-dependent manner at drug concentrations from IC80 to 10-fold IC80, and the levels at the 10-fold IC80 were significantly higher (P<0.05) than those at IC80. The concentration dependency on GLP-1 increment was also confirmed based on the experiment in which the endogenous active GLP-1 levels were measured after an oral carbohydrate load. These findings suggest that an almost complete inhibition (80%) of plasma DPP-4 activity was insufficient to protect GLP-1 degradation, and much higher drug concentrations such as 10-fold IC80 are necessary to potently protect GLP-1 from degradation by DPP-4 commonly present in blood and tissues.

Key words

anagliptin - dipeptidyl peptidase-4 inhibitor - continuous infusion - steady state active GLP-1 level - 80% inhibitory concentration
 

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