Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 36, 2006 - Issue 4
109
Views
5
CrossRef citations to date
0
Altmetric
Research Article

Pharmacokinetics and clearance processes of UK-279,276 (rNIF) in rat and dog: Comparison with human data

, , &
Pages 341-349 | Received 05 Dec 2005, Published online: 22 Sep 2008
 

Abstract

UK-279,276, or recombinant neutrophil inhibitory factor (rNIF), is a glycoprotein that binds to the human CD11b receptor (IC50 = <0.5 nM) and inhibits neutrophil binding to vascular endothelial cells. In dogs, the pharmacokinetics of UK-279,276 are non-linear with clearance slowing as dose increases (apparent clearance 0.06 ml min−1 kg−1 at 0.l mg kg−1 decreasing to 0.02 ml min−1 kg−1 at 2 mg kg−1). The observations are in keeping with human pharmacokinetic data. In rats, clearance is linear (0.07–0.13 ml min−1 kg−1) across a similar dose range (0.006–2.25 mg kg−1) compared with dogs and humans. These data indicate that two clearance processes act on UK-279,276 in dogs and humans, but only one clearance process occurs in rats. A non-saturable, low-affinity/high-capacity clearance process is present in all animal species studied as well as in human, and it is believed to be hepatic uptake mediated by the asialoglycoprotein receptor. A second, saturable, clearance process is present in dogs and humans that is not apparent in the rat. This high-affinity/low-capacity process is thought to be mediated by interaction with the CD11b receptor, which is the pharmacological target for this molecule. This hypothesis is supported by the marked species differences seen for the affinity of CD11b for UK-279,276, with dogs and humans having high-affinity (IC50 = <0.5 nM), whilst the rat affinity is low (IC50 = 134 nM).

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 897.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.