Pharmacokinetics of tiaprofenic acid in normal rabbits and rabbits subjected to joint immobilisation.
In a previous study, tiaprofenic acid (TA) was administered daily over a 30-day period at 5 and 10 mg/kg of body weight subcutaneously (s.c.) to animals with arthritis induced by immobilisation. The 10 mg/kg dose exacerbated the loss of proteoglycan from joint cartilage but the 5 mg/kg dose showed protective effects on articular cartilage. These results led us to investigate the concentration of TA achieved in synovial fluid of both the immobilised and non-immobilised rabbit joints after single s.c. doses of 5 or 10 mg/kg. The half-lives of elimination of TA from the synovial fluids of the immobilised joints were 1.27 and 1.07 h after the 5 and 10 mg doses, respectively, and 0.66 and 0.39 h in the non-immobilised contralateral joints. Clearances from synovial fluid to plasma were found to be 0.41 and 0.55 ml/h/kg from the immobilised joints after the 5 and 10 mg doses, respectively, and 0.11 and 0.25 ml/h/kg from the non-immobilised contralateral joints. The peak concentration of TA achieved in synovial fluid of immobilised knee joints after a single s.c. injection of 10 mg/kg was approximately two times greater than the concentrations achieved after administration of 5 mg/kg by the same route and two to six times greater than the levels achieved after oral administration of TA at 600 mg/day in humans.
Meyer-Carrive
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Raymond Purves and Bone and Joint Research Laboratories (University of Sydney), Royal North Shore Hospital of Sydney, St. Leonards, NSW, Australia.
Graham
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Ghosh
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D007103:Immobilization; D007202:Indicators and Reagents; D007596:Joints / Q000502:physiology; D011422:Propionates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D013582:Synovial Fluid / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011422:Propionates; C021270:tiaprofenic acid