title: Local tolerance of intraarticular administration of lornoxicam into the rabbit knee joint.
abstract: The local tolerability of lornoxicam (Xefo) after single and repeated intraarticular administration was assessed in the rabbit and compared to established standard therapies (hyaluronic acid--Synvisc and the glucocorticoid triamcinolone--Triam), and the results are discussed in the context of the literature. Two local tolerance studies were performed using five male rabbits per group. Lornoxicam and competitor products were administered into the right knee joint in a volume of 500 μL. The contralateral left knee joint of the same animal was used as the control and was injected with water for injection. Three out of five animals were killed 72 h after the last administration, whereas the remaining two animals were subjected to a 2- or 6-week recovery period in the first and the second study, respectively. Findings revealed adaptive changes related to the mechanical irritation of the injection and to adaptive responses of the synoviocytes, but no signs of toxicity to bone or chondrotoxicity. Toxicokinetic analysis showed a fast and almost complete absorption of lornoxicam from the joints into the systemic circulation. As a conclusion, repeated intraarticular administration of lornoxicam was well tolerated in rabbits.
authors.affiliation: Nycomed GmbH, Institute of Pharmacology and Preclinical Drug Safety, Haidkrugsweg 1, 22885 Barsbuettel, Germany. susanne.schroeder@nycomed.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Schroeder
authors.forename: Anke
authors.initials: A
authors.lastname: Heuser
authors.forename: Arn
authors.initials: A
authors.lastname: Tellmann
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Goebel
authors.forename: Thomas
authors.initials: T
authors.lastname: Woehrmann
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018771:Arthralgia / Q000517:prevention & control; D001842:Bone and Bones / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D006984:Hypertrophy; D007270:Injections, Intra-Articular / Q000009:adverse effects*; D007719:Knee Joint / Q000473:pathology*; D008297:Male; D010894:Piroxicam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D013583:Synovial Membrane / Q000473:pathology*; D014221:Triamcinolone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C049816:hylan; D010894:Piroxicam; D014221:Triamcinolone; D006820:Hyaluronic Acid; C059451:lornoxicam