Influence of hepatic impairment on pharmacokinetics of the human GLP-1 analogue, liraglutide.

摘要

AIMS: To compare the pharmacokinetics (PK) of a single-dose of liraglutide in subjects with hepatic impairment. METHODS: This parallel group, open label trial involved four groups of six subjects with healthy, mild, moderate and severe hepatic impairment, respectively. Each subject received 0.75 mg of liraglutide (s.c., thigh), and blood samples were taken over 72 h for PK assessment. Standard laboratory and safety data were collected. The primary endpoint was area under the plasma liraglutide concentration-time curve from time zero to infinity (AUC(0,infinity)). RESULTS: Exposure to liraglutide was not increased by hepatic impairment. On the contrary, mean AUC(0,infinity) was highest for healthy subjects and lowest for subjects with severe hepatic impairment (severe/healthy: 0.56, with 90% CI 0.39, 0.81) and equivalence in this parameter across groups was not demonstrated. C(max) also tended to decrease with hepatic impairment (severe/healthy: 0.71, with 90% CI 0.52, 0.97), but t(max) was similar across groups (11.3-13.2 h). There were no serious adverse events, hypoglycaemic episodes or clinically significant changes in laboratory parameters and liraglutide was considered well tolerated. CONCLUSIONS: This study indicated no safety concerns regarding use of liraglutide in patients with hepatic impairment. Exposure to liraglutide was not increased by impaired liver function; rather, the results suggest a decreased exposure with increasing degree of hepatic impairment. However, data are not conclusive to suggest a dose increase of liraglutide. Thus, the results indicate that patients with type 2 diabetes mellitus and hepatic impairment can use standard treatment regimens of liraglutide. There is, however, currently limited clinical experience with liraglutide in patients with hepatic impairment.