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Xenobiotica
the fate of foreign compounds in biological systems
Volume 39, 2009 - Issue 2
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Research Article

Pharmacokinetics and disposition of recombinant human osteoprotegerin (rhOPG) after intravenous administration in female fischer rats

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Pages 113-124 | Received 18 Sep 2008, Accepted 30 Oct 2008, Published online: 01 Feb 2009
 

Abstract

  1. Osteoprotegerin (OPG) is a secreted member of the tumour necrosis factor receptor (TNFR) family that leads to the suppression of the differentiation, activation and survival of osteoclasts. The objective was to investigate the in vivo pharmacokinetics and tissue distribution of full-length recombinant human OPG (rhOPG) as well as its clearance mechanism using 125I-labelled protein (125I-rhOPG) after intravenous administration to female Fischer rats.

  2. 2. 125I-rhOPG was rapidly and predominantly distributed to the liver after dosing (3 mg kg−1). Immunohistochemical analysis indicated that rhOPG was located in the sinusoids of the liver.

  3. The hepatic uptake of 125I-rhOPG (0.01 mg kg−1) was partly regulated under a saturable process. Pre-dosing of some sulfated glycans (20 mg kg−1), especially dextran sulfate, heparin and fucoidan, markedly inhibited the hepatic uptake of 125I-rhOPG. The clearance of 125I-rhOPG was markedly reduced by the conjugation of dextran sulfate.

  4. The results suggested that the hepatic clearance of 125I-rhOPG was mainly mediated by the interaction with glycosaminoglycans.

Acknowledgements

The authors would like to thank Dr Kenichi Sudo for helpful insights.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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