Volume 7 Supplement 2

13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)

Open Access

Influence of the Duffy genotype on pharmacokinetics and pharmacodynamics of recombinant monocyte chemoattractant protein (MCP-1) in vivo

  • Florian B Mayr1,
  • Alexander O Spiel1,
  • Judith M Leitner1,
  • Christa Firbas1,
  • Janet Schnee2,
  • James Hilbert2 and
  • Bernd Jilma1Email author
BMC Pharmacology20077(Suppl 2):A31

DOI: 10.1186/1471-2210-7-S2-A31

Published: 14 November 2007

Monocyte chemoattractant protein-1 (MCP-1) binds to the Duffy antigen (Fy) on erythrocytes, which may act as a sink for several chemokines including MCP-1. We hypothesized that infusion of MCP-1 could result in different pharmacokinetics of MCP and possibly altered pharmacodynamics between Duffy positive and negative individuals. The primary aim of this trial was to compare pharmacokinetics of MCP-1 between Duffy positive and Duffy negative individuals under infusion of recombinant human MCP-1. This was a randomized, double-blinded, placebo-controlled dose escalation trial in 36 healthy volunteers. Subjects received infusions of 0.02–2.0 μg/kg MCP-1 or placebo for one hour. MCP-1 displayed linear pharmacokinetics. Duffy negative individuals reached maximal plasma levels earlier, but plasma concentration profiles were not altered. MCP-1 markedly increased monocyte counts, and estimated EC50 values were 10-fold higher in Duffy positive than Duffy negative subjects. Increased monocyte counts were associated with decreased surface expression of intercellular adhesion molecule 1 (ICAM-1, CD54). In contrast, MCP-1 neither altered CCR-2 or CD11b surface expression nor markers of platelet or endothelial activation, inflammation and coagulation. MCP-1 acts as a highly selective chemoattractant for monocytes in humans. The Duffy antigen had minimal effects on pharmacokinetics of MCP-1, but may affect EC50 values.

Authors’ Affiliations

(1)
Department of Clinical Pharmacology, Medical University of Vienna
(2)
Boehringer Ingelheim

Copyright

© Mayr et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.

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