Population pharmacokinetics of liraglutide, a once-daily human glucagon-like peptide-1 analog, in healthy volunteers and subjects with type 2 diabetes, and comparison to twice-daily exenatide

Journal of Clinical Pharmacology
Estelle WatsonSteen H Ingwersen

Abstract

The once-daily human glucagon-like peptide-1 (GLP-1) analog, liraglutide, was recently shown to provide improved glycemic control in subjects with type 2 diabetes (T2D) compared with exenatide. The aim of this work is to estimate the population pharmacokinetics of liraglutide and make a comparison to the pharmacokinetic profile of exenatide. Pharmacokinetic data from 5 published studies of subcutaneous and intravenous administration of liraglutide to healthy volunteers (HV) and subjects with T2D were used to develop a population pharmacokinetic model in NONMEM. Exenatide data came from a published study in T2D. Liraglutide pharmacokinetics were adequately described using a 1-compartment model with sequential zero- and first-order absorption. The pharmacokinetic profile of once-daily liraglutide showed considerably smaller peak-to-trough fluctuations compared with twice-daily exenatide. A small difference in the estimates of absorption parameters was found between HV and subjects with T2D but was not clinically relevant. It was concluded that pharmacokinetic profiles estimated by modeling showed that liraglutide has pharmacokinetic properties consistent with once-daily dosing in humans and provides better pharmacokinetic coverag...Continue Reading

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Citations

Sep 24, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jang Kyoung KimYong-Hee Kim
Dec 18, 2015·BBA Clinical·Marjolein K SechterbergerJ Hans DeVries
Sep 20, 2011·Pharmacotherapy·Evan M Sisson
Nov 26, 2015·Clinical Pharmacokinetics·Lisbeth V JacobsenSteen H Ingwersen
Aug 15, 2015·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Annachiara UccellatoreAntonio Ceriello
Jan 13, 2015·Molecular and Cellular Endocrinology·Giulia CantiniMichaela Luconi
Oct 21, 2016·Clinical Pharmacokinetics·Rune V OvergaardChristine B Jensen
Oct 19, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ying WangGeorge B Benedek
Sep 22, 2016·British Journal of Clinical Pharmacology·Brenda Cirincione, Donald E Mager
Aug 30, 2018·Diabetes/metabolism Research and Reviews·Raffaella GentilellaAgostino Consoli
Feb 23, 2019·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Rune V OvergaardSteen H Ingwersen
Jul 8, 2011·American Journal of Therapeutics·Kyle R Peters
Sep 1, 2016·Expert Review of Endocrinology & Metabolism·Katherine G MooreJennifer N Clements
Feb 7, 2019·Scientific Reports·Richard RaubertasCai Li
Mar 3, 2019·International Journal of Molecular Sciences·Michał WicińskiKatarzyna Pawlak-Osińska

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