Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct® )

Drugs in R&D
Inga BjørnsdottirOla Sternebring

Abstract

Extended half-life (EHL) factor VIII (FVIII)-replacement therapies enable patients with haemophilia A to maintain higher activity levels with fewer injections. N8-GP (turoctocog alfa pegol; Esperoct®) is an EHL product derived from conjugation of polyethylene glycol (PEG) to a recombinant FVIII protein. Upon activation, PEG is released from the active protein and excreted in urine and faeces. While PEG levels are expected to reach steady state with repeated dosing, there has been some discussion regarding whether abnormal accumulation of PEG in plasma and tissues may occur. Our objective was to examine plasma PEG concentrations in rats and humans repeatedly treated with N8-GP for periods of up to 5 years. PEG levels were measured using liquid chromatography-tandem mass spectrometry in plasma samples from rats treated with N8-GP as part of a 52-week toxicity study. Human plasma samples from children, adolescents and adults treated with N8-GP as part of the pathfinder programme were also examined (NCT01731600; NCT01480180). These data were compared with steady-state PEG levels predicted by pharmacokinetic modelling of single-dose rat data. PEG levels reached steady state in plasma in both rats and humans after repeated dosing. Th...Continue Reading

References

Oct 26, 2005·Drug Discovery Today·Francesco M Veronese, Gianfranco Pasut
Jul 8, 2010·Blood Transfusion = Trasfusione Del Sangue·Anna Maria TimperioLello Zolla
Jul 11, 2012·Haemophilia : the Official Journal of the World Federation of Hemophilia·A SrivastavaUNKNOWN Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia
Nov 2, 2012·Paediatrics & Child Health·Shinya Ito
Jun 15, 2014·Drug Discovery Today·Andreas BaumannJennifer Sims
Nov 1, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Inga BjørnsdottirMorten A Bagger
Feb 13, 2016·Journal of Pharmaceutical Sciences·Peter L TurecekInge A Ivens
Dec 3, 2016·Thrombosis and Haemostasis·Paul GiangrandeUNKNOWN Pathfinder™2 Investigators
May 2, 2017·Journal of Toxicology·Caroline E RasmussenHanne Offenberg
May 12, 2018·Haemophilia : the Official Journal of the World Federation of Hemophilia
Jan 18, 2019·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Andreas BaumannThomas Schwarz
Sep 25, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ola SternebringInga Bjørnsdottir

❮ Previous
Next ❯

Clinical Trials Mentioned

NCT01480180
NCT01731600

Software Mentioned

Analyst
pathfinder
pathfinder2

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.