Cargando…

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

BACKGROUND: 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 recombin...

Descripción completa

Detalles Bibliográficos
Autores principales: Bjørnsdottir, Inga, Støvring, Birgitte, Søeborg, Tue, Jacobsen, Helene, Sternebring, Ola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221073/
https://www.ncbi.nlm.nih.gov/pubmed/32152818
http://dx.doi.org/10.1007/s40268-020-00297-1
_version_ 1783533292752994304
author Bjørnsdottir, Inga
Støvring, Birgitte
Søeborg, Tue
Jacobsen, Helene
Sternebring, Ola
author_facet Bjørnsdottir, Inga
Støvring, Birgitte
Søeborg, Tue
Jacobsen, Helene
Sternebring, Ola
author_sort Bjørnsdottir, Inga
collection PubMed
description BACKGROUND: 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. OBJECTIVE: Our objective was to examine plasma PEG concentrations in rats and humans repeatedly treated with N8-GP for periods of up to 5 years. METHODS: 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. RESULTS: PEG levels reached steady state in plasma in both rats and humans after repeated dosing. The timing and degree of PEG increase to steady state were in line with or below model predictions, confirming the utility of the pharmacokinetic model and indicating that rat data can be used to estimate human plasma PEG levels. CONCLUSION: Steady-state PEG levels were reached in plasma from rats and humans repeatedly treated with N8-GP. No unexpected increase in PEG was observed.
format Online
Article
Text
id pubmed-7221073
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-72210732020-05-15 Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®)) Bjørnsdottir, Inga Støvring, Birgitte Søeborg, Tue Jacobsen, Helene Sternebring, Ola Drugs R D Original Research Article BACKGROUND: 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. OBJECTIVE: Our objective was to examine plasma PEG concentrations in rats and humans repeatedly treated with N8-GP for periods of up to 5 years. METHODS: 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. RESULTS: PEG levels reached steady state in plasma in both rats and humans after repeated dosing. The timing and degree of PEG increase to steady state were in line with or below model predictions, confirming the utility of the pharmacokinetic model and indicating that rat data can be used to estimate human plasma PEG levels. CONCLUSION: Steady-state PEG levels were reached in plasma from rats and humans repeatedly treated with N8-GP. No unexpected increase in PEG was observed. Springer International Publishing 2020-03-09 2020-06 /pmc/articles/PMC7221073/ /pubmed/32152818 http://dx.doi.org/10.1007/s40268-020-00297-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Original Research Article
Bjørnsdottir, Inga
Støvring, Birgitte
Søeborg, Tue
Jacobsen, Helene
Sternebring, Ola
Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®))
title Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®))
title_full Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®))
title_fullStr Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®))
title_full_unstemmed Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®))
title_short Plasma Polyethylene Glycol (PEG) Levels Reach Steady State Following Repeated Treatment with N8-GP (Turoctocog Alfa Pegol; Esperoct(®))
title_sort plasma polyethylene glycol (peg) levels reach steady state following repeated treatment with n8-gp (turoctocog alfa pegol; esperoct(®))
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221073/
https://www.ncbi.nlm.nih.gov/pubmed/32152818
http://dx.doi.org/10.1007/s40268-020-00297-1
work_keys_str_mv AT bjørnsdottiringa plasmapolyethyleneglycolpeglevelsreachsteadystatefollowingrepeatedtreatmentwithn8gpturoctocogalfapegolesperoct
AT støvringbirgitte plasmapolyethyleneglycolpeglevelsreachsteadystatefollowingrepeatedtreatmentwithn8gpturoctocogalfapegolesperoct
AT søeborgtue plasmapolyethyleneglycolpeglevelsreachsteadystatefollowingrepeatedtreatmentwithn8gpturoctocogalfapegolesperoct
AT jacobsenhelene plasmapolyethyleneglycolpeglevelsreachsteadystatefollowingrepeatedtreatmentwithn8gpturoctocogalfapegolesperoct
AT sternebringola plasmapolyethyleneglycolpeglevelsreachsteadystatefollowingrepeatedtreatmentwithn8gpturoctocogalfapegolesperoct