Pharmacokinetic and pharmacodynamic interactions between palifermin and heparin

Bing Bing Yang, Brad Gillespie, Brian Smith, William Smith, Agneta Lissmats, Mattias Rudebeck, Torbjörn Kullenberg, Birgitta Olsson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Oral mucositis, a severe complication during chemo- and/or radiotherapy, is prevented with palifermin treatment, a recombinant human keratinocyte growth factor (KGF/FGF-7). The FGF family belongs to the larger family of heparin-binding growth factors. Because it has been shown that heparin modulates binding of KGF to the KGF receptor and subsequently affects cellular proliferation induced by the KGF mitogenic signal, it is critical to understand the drug-drug interactions between palifermin and heparin, particularly because of heparin's narrow therapeutic margin. Two studies were performed in healthy subjects to characterize the effect of palifermin on the pharmacodynamics of heparin (activated partial thromboplastin time) and evaluate the impact of heparin on the pharmacokinetics and pharmacodynamics (Ki67 staining of buccal mucosal tissue) of palifermin. Results demonstrated a pronounced pharmacokinetic interaction; heparin coadministration increased the palifermin AUC 4- to 5-fold and decreased its half-life by 40%-45%, suggesting an approximate 70%-80% decrease in palifermin clearance and volume of distribution. These changes in the pharmacokinetics of palifermin during coadministration of heparin, however, did not affect the pharmacodynamic effect of palifermin, or the anticoagulant activity of heparin, and did not lead to increased safety findings. Therefore, these results suggest that dose adjustments for heparin and palifermin are not warranted when administered concurrently.

Original languageEnglish (US)
Pages (from-to)1109-1118
Number of pages10
JournalJournal of clinical pharmacology
Volume55
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Fibroblast Growth Factor 7
Heparin
Pharmacokinetics
Stomatitis
Partial Thromboplastin Time
Cheek
Drug Interactions
Anticoagulants
Area Under Curve
Half-Life
Intercellular Signaling Peptides and Proteins
Healthy Volunteers
Mucous Membrane
Radiotherapy
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Yang, B. B., Gillespie, B., Smith, B., Smith, W., Lissmats, A., Rudebeck, M., ... Olsson, B. (2015). Pharmacokinetic and pharmacodynamic interactions between palifermin and heparin. Journal of clinical pharmacology, 55(10), 1109-1118. https://doi.org/10.1002/jcph.516

Pharmacokinetic and pharmacodynamic interactions between palifermin and heparin. / Yang, Bing Bing; Gillespie, Brad; Smith, Brian; Smith, William; Lissmats, Agneta; Rudebeck, Mattias; Kullenberg, Torbjörn; Olsson, Birgitta.

In: Journal of clinical pharmacology, Vol. 55, No. 10, 01.10.2015, p. 1109-1118.

Research output: Contribution to journalArticle

Yang, BB, Gillespie, B, Smith, B, Smith, W, Lissmats, A, Rudebeck, M, Kullenberg, T & Olsson, B 2015, 'Pharmacokinetic and pharmacodynamic interactions between palifermin and heparin', Journal of clinical pharmacology, vol. 55, no. 10, pp. 1109-1118. https://doi.org/10.1002/jcph.516
Yang, Bing Bing ; Gillespie, Brad ; Smith, Brian ; Smith, William ; Lissmats, Agneta ; Rudebeck, Mattias ; Kullenberg, Torbjörn ; Olsson, Birgitta. / Pharmacokinetic and pharmacodynamic interactions between palifermin and heparin. In: Journal of clinical pharmacology. 2015 ; Vol. 55, No. 10. pp. 1109-1118.
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