Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Sensitivity of Pegfilgrastim Pharmacokinetic and Pharmacodynamic Parameters to Product Differences in Similarity Studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Pharmetheus, Uppsala, Sweden.ORCID iD: 0000-0002-8109-3426
Dr Reddys Labs, Basel, Switzerland.
Pharmetheus, Uppsala, Sweden.
Pharmetheus, Uppsala, Sweden.
Show others and affiliations
2019 (English)In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 21, no 5, article id 85Article in journal (Refereed) Published
Abstract [en]

In this work, a previously developed pegfilgrastim (PG) population pharmacokinetic-pharmacodynamic (PKPD) model was used to evaluate potential factors of importance in the assessment of PG PK and PD similarity. Absolute neutrophil count (ANC) was the modelled PD variable. A two-way cross-over study was simulated where a reference PG and a potentially biosimilar test product were administered to healthy volunteers. Differences in delivered dose amounts or potency between the products were simulated. A different baseline absolute neutrophil count (ANC) was also considered. Additionally, the power to conclude PK or PD similarity based on areas under the PG concentration-time curve (AUC) and ANC-time curve (AUEC) were calculated. Delivered dose differences between the products led to a greater than dose proportional differences in AUC but not in AUEC, respectively. A 10% dose difference from a 6mg dose resulted in 51% and 7% differences in AUC and AUEC, respectively. These differences were more pronounced with low baseline ANC. Potency differences up to 50% were not associated with large differences in either AUCs or AUECs. The power to conclude PK similarity was affected by the simulated dose difference; with a 4% dose difference from 6mg the power was approximately 29% with 250 subjects. The power to conclude PD similarity was high for all delivered dose differences and sample sizes.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 21, no 5, article id 85
Keywords [en]
biosimilarity, exposure sensitivity, granulocyte colony-stimulating factor, pegfilgrastim, population pharmacokinetic-pharmacodynamic modelling
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-390375DOI: 10.1208/s12248-019-0349-3ISI: 000475610900002PubMedID: 31286293OAI: oai:DiVA.org:uu-390375DiVA, id: diva2:1341804
Available from: 2019-08-12 Created: 2019-08-12 Last updated: 2019-08-12Bibliographically approved

Open Access in DiVA

fulltext(1486 kB)49 downloads
File information
File name FULLTEXT01.pdfFile size 1486 kBChecksum SHA-512
01ff2fb8d3bcfbe073d630795462209c796f11735f0dfd92df6c1fc75633a063bc8757a030c477fc7550d660e0a3f7618fcf65c53c5d212b2019eebfc7fdeb2d
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Brekkan, AriKarlsson, Mats
By organisation
Department of Pharmaceutical Biosciences
In the same journal
AAPS Journal
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 49 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 88 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf