Disposition of human recombinant lubricin in naive rats and in a rat model of post-traumatic arthritis after intra-articular or intravenous administration.
AAPS J
; 14(1): 97-104, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22228117
ABSTRACT
We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB1, 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]LUB1 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]LUB1 binding to its ligands. [(125)I]LUB1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB1 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, LUB1 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Glicoproteínas
/
Articulação do Joelho
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article