Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synergism in pharmacokinetics of retagliptin and metformin observed during clinical trials of their combination therapy

Xiaolan Yong¹, Tingting Hu¹, Shiyin Feng¹, Xiaolin Du¹, Huiqing Shi¹, Wang Feng²

¹Department of Clinical Pharmacy, The General Hospital of Chendu Military Area Command; ²Jiangsu Hengrui Medicine Co Ltd, No. 145 Renming East Road, Lianyunggang City, Jiangsu Province, China.

For correspondence:- Wang Feng Email: wangfeng8799@163.com Tel:+865185465745

Received: 29 December 2014 Accepted: 27 June 2015 Published: 30 August 2015

Citation: Yong X, Hu T, Feng S, Du X, Shi H, Feng W. Synergism in pharmacokinetics of retagliptin and metformin observed during clinical trials of their combination therapy. Trop J Pharm Res 2015; 14(8):1481-1486 doi: 10.4314/tjpr.v14i8.22

© 2015 The authors.
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Abstract

Purpose: To investigate the safety and potential pharmacokinetic (PK) interaction between retagliptin, a selective inhibitor of dipeptidyl peptidase-4, and metformin in healthy subjects.

Methods: In open-label, randomized, three-period, three-treatment crossover studies, 15 subjects received 100 mg retagliptin, 1500 mg metformin or the combination. The area under the curve from the time of dosing to infinity (AUC_inf) and the maximum observed plasma concentration (C_max) of each drug were measured.

Results: The combination of retagliptin and metformin did not result in clinically significant alterations in the pharmacokinetics of SP2086 or metformin. The AUC_inf and C_max of retagliptin co-administered with metformin were 16.49 and 25.88 % higher than for retagliptin alone, respectively, while the AUC_inf of metformin co-administered with retagliptin was 22.06 % higher than for metformin alone. The 90 % confidence interval of both glucose-lowering drugs’ AUC_inf and C_max of the geometric mean ratios of SP2086 + metformin fell within the pre-specified interval of 80 - 125 %. No laboratory adverse conditions occurred during the study. Retagliptin appeared generally safe and well-tolerated when administered alone or in combination with metformin.

Conclusion: The results may be an indication that no dose adjustments are likely to be required when retagliptin is given in combination with metformin.

Keywords: Retagliptin, Metformin, Pharmacokinetic interaction, Synergism, Type 2 diabetes