Disposition of Human Recombinant Lubricin in Naive Rats and in a Rat Model of Post-traumatic Arthritis After Intra-articular or Intravenous Administration
| Autor: | Xin Xu, Yulia Vugmeyster, Richard Zollner, Jian Li, Qin Wang, Carl R. Flannery, M.A. Rivera-Bermudez, Daren Daugusta, John M. Harrold |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Knee Joint Rat model Pharmaceutical Science Arthritis Alpha (ethology) Osteoarthritis CHO Cells law.invention Injections Intra-Articular Cricetulus Pharmacokinetics law Internal medicine Cricetinae medicine Animals Humans Tissue Distribution Glycoproteins business.industry Half-life Disposition medicine.disease Arthritis Experimental Recombinant Proteins Surgery Rats Endocrinology Rats Inbred Lew Injections Intravenous Recombinant DNA Autoradiography Female business Research Article Half-Life |
| Popis: | 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, [(125)I]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 [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]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. |
| Databáze: | OpenAIRE |
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