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Effect of varying degrees of renal impairment on the pharmacokinetics and tolerability of taspoglutide

Authors :
Markus Niggli
Christophe Schmitt
Mylene Giraudon
Nathalie Lambert
Bernhard Mangold
Stefan Sturm
Jochen Brumm
Source :
Diabetes, Obesity and Metabolism. 19:537-544
Publication Year :
2017
Publisher :
Wiley, 2017.

Abstract

Aim To evaluate single-dose pharmacokinetics and tolerability of taspoglutide in people with varying degrees of renal impairment and matched healthy participants. Methods Participants in the present study were people with mild renal impairment (n = 10), moderate impairment (n = 10), severe impairment (n = 9), and a matched healthy control group (n = 10). Participants received a single subcutaneous injection of taspoglutide (10 mg) on day 1. Plasma and urine drug concentration, antibody formation, vital signs, ECGs and routine laboratory variables were measured frequently and adverse events (AEs) were monitored for 9 weeks. Results Taspoglutide exposure was higher among participants with moderate and severe renal impairment compared with participants with normal renal function. Mean AUClast was 13% and 38% higher in participants with moderate and severe renal impairment, respectively compared with participants with normal renal function. Likewise, mean peak plasma concentration (Cmax ) was 57% and 93% higher in participants with moderate and severe renal function impairment, respectively, compared with participants with normal renal function. Linear regression analyses showed a statistically significant inverse relationship between taspoglutide exposure parameters (AUC and Cmax ) and creatinine clearance. Higher incidences of gastrointestinal (GI) AEs were reported in participants with severe renal impairment. Conclusion Renal impairment altered the pharmacokinetics of taspoglutide. The degree of renal impairment was associated with an increased exposure to taspoglutide and an increased risk of GI AEs.

Details

ISSN :
14628902
Volume :
19
Database :
OpenAIRE
Journal :
Diabetes, Obesity and Metabolism
Accession number :
edsair.doi...........9dbf84c40ae6abb9e6f913f9cbc79f42
Full Text :
https://doi.org/10.1111/dom.12850