PHARMACOKINETICS OF TIAPROFENIC ACID IN NORMAL RABBITS AND RABBITS SUBJECTED TO JOINT IMMOBILIZATION

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 do se exacerbated the loss of proteoglycan from joint cartilage but the 5 mg/kg dose showed protective effects on articular cartilage. These re sults led us to investigate the concentration of TA achieved in synovi al fluid of both the immobilised and non-immobilised rabbit joints aft er single s.c. doses of 5 or 10 mg/kg. The half-lives of elimination o f 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 immobi lised joints after the 5 and 1 0 mg doses, respectively, and 0.11 and 0.25 ml/h/kg from the non-immobilised contralateral joints. The peak c oncentration of TA achieved in synovial fluid of immobilised knee join ts after a single s.c. injection of 10 mg/kg was approximately two tim es greater than the concentrations achieved after administration of 5 mg/kg by the same route and two to six times greater than the levels a chieved after oral administration of TA at 600 mg/day in humans.