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The AAPS Journal

, Volume 14, Issue 1, pp 97–104 | Cite as

Disposition of Human Recombinant Lubricin in Naive Rats and in a Rat Model of Post-traumatic Arthritis After Intra-articular or Intravenous Administration

  • Yulia VugmeysterEmail author
  • Qin Wang
  • Xin Xu
  • John Harrold
  • Daren Daugusta
  • Jian Li
  • Richard Zollner
  • Carl R. Flannery
  • Moisés A. Rivera-Bermúdez
Research Article

Abstract

We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [125I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [125I]LUB:1 binding to its ligands. [125I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [125I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [125I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t 1/2) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

Key words

lubricin osteoarthritis pharmacokinetics 

Notes

Acknowledgments

Authors thank David Defranco, Jennifer Spencer-Pierce, Cyndi Filliettaz, Adam Root, Tracey Blanchet, Vikram Patel, and Sonya Glasson for their assistance with these studies.

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Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Yulia Vugmeyster
    • 1
    Email author
  • Qin Wang
    • 1
    • 4
  • Xin Xu
    • 1
    • 5
  • John Harrold
    • 1
  • Daren Daugusta
    • 2
  • Jian Li
    • 2
  • Richard Zollner
    • 3
  • Carl R. Flannery
    • 2
  • Moisés A. Rivera-Bermúdez
    • 2
  1. 1.Department of Pharmacokinetics, Dynamics, and MetabolismPfizer IncAndoverUSA
  2. 2.Department of Tissue RepairPfizer IncCambridgeUSA
  3. 3.Department of Global Biotherapeutics TechnologiesPfizer IncCambridgeUSA
  4. 4.Department of Drug Metabolism and Pre-Clinic Drug SafetyBiogenidecCambridgeUSA
  5. 5.Center for Translational TherapeuticsNational Institutes of HealthRockvilleUSA

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