Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 May;72(5):563-72.
doi: 10.1007/s00228-016-2017-1. Epub 2016 Feb 9.

Effect of hepatic or renal impairment on the pharmacokinetics of evacetrapib

David S Small  1 , Wei Zhang  2 , Jane Royalty  3 , Ellen A Cannady  2 , Delyn Downs  2 , Demetrio Ortega  2 , Jeffrey G Suico  2
Affiliations
Clinical Trial

Effect of hepatic or renal impairment on the pharmacokinetics of evacetrapib

David S Small et al. Eur J Clin Pharmacol. 2016 May.

Abstract

Purpose: The aim of this study is to investigate the effect of hepatic or renal impairment on the pharmacokinetics of a single 130-mg evacetrapib dose.

Methods: Two open-label, parallel-design studies in males and females with normal hepatic function or Child-Pugh mild, moderate, or severe hepatic impairment, or with normal renal function or severe renal impairment. Non-compartmental pharmacokinetic parameters were estimated from plasma concentration-time data. Evacetrapib safety and tolerability were assessed.

Results: Pharmacokinetic parameter estimates were comparable between controls and mildly hepatically impaired subjects. Geometric mean area under the concentration-time curve (AUC) was greater, half-life (t1/2) was longer, and maximum concentration (Cmax) was lower in subjects with moderate and severe hepatic impairment than in controls. Apparent clearance (CL/F) did not differ between controls and those with mild hepatic impairment, but CL/F decreased for moderate and severe impairment. Spearman correlation coefficient showed no relationship between CL/F and Child-Pugh score. In the renal study, AUC and t1/2 were similar between groups, while Cmax was 15 % lower in subjects with severe impairment. CL/F in severely renally impaired subjects differed by <6 % from that in controls. Spearman correlation coefficient showed no apparent relationship between CL/F and estimated creatinine clearance or glomerular filtration rate. Neither study noted changes in clinical laboratory parameters or clinically significant findings. Adverse event incidence was low, and all were mild or moderate in severity.

Conclusion: Evacetrapib exposure did not differ between mild hepatic impairment and normal hepatic function, but increased along the progression from mild to moderate to severe hepatic impairment. Severe renal impairment did not affect evacetrapib exposure.

Keywords: Cholesteryl ester transfer protein; Evacetrapib; Hepatic impairment; Pharmacokinetics; Renal impairment.

PubMed Disclaimer

Figures

Fig 1
Fig 1
Arithmetic mean plasma concentration-time profiles of evacetrapib following a single dose of 130-mg evacetrapib in subjects with mild, moderate, and severe hepatic impairment and control subjects with normal hepatic function
Fig 2
Fig 2
Relationship between evacetrapib apparent clearance (CL/F) and Child-Pugh score
Fig 3
Fig 3
Arithmetic mean plasma concentration-time profiles of evacetrapib following a single dose of 130-mg evacetrapib in subjects with severe renal impairment and control subjects with normal renal function
Fig 4
Fig 4
Relationship between evacetrapib apparent clearance (CL/F) and creatinine clearance (CLcr) estimated by Cockcroft-Gault equation (upper panel) and glomerular filtration rate (eGFR) estimated using the Modification of Diet in Renal Disease (MDRD) equation (lower panel)
See this image and copyright information in PMC

References

    1. Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, Kastelein JJ, Bittner V, Fruchart JC, Treating to New Targets Investigators HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357(13):1301–1310. doi: 10.1056/NEJMoa064278. - DOI - PubMed
    1. Emerging Risk Factors Collaboration. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, KK R, Thompson A, AM W, Lewington S, Sattar N, CJ P, Collins R, SG T, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. Jama. 2009;302(18):1993–2000. doi: 10.1001/jama.2009.1619. - DOI - PMC - PubMed
    1. Cholesterol Treatment Trialists’ Collaboration. Baigent C, Blackwell L, Emberson J, LE H, Reith C, Bhala N, Peto R, EH B, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–1681. doi: 10.1016/S0140-6736(10)61350-5. - DOI - PMC - PubMed
    1. Bays H, Stein EA. Pharmacotherapy for dyslipidaemia—current therapies and future agents. Expert Opin Pharmacother. 2003;4:1901–1938. doi: 10.1517/14656566.4.11.1901. - DOI - PubMed
    1. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62:707–714. doi: 10.1016/0002-9343(77)90874-9. - DOI - PubMed

Publication types

LinkOut - more resources