Transsynovial distribution and protein binding of pirazolac in patients with rheumatoid arthritis.
Following a washout period of 7 days, twenty-one patients suffering from rheumatoid arthritis and 3 from osteo-arthritis, who all required articular puncture were given a non-steroidal anti-inflammatory drug pirazolac 450 mg b.d. for 7 days. After discontinuation of the treatment the subjects were divided into 4 groups each of 6 patients. The non protein bound fraction of pirazolac in synovial fluid (0.86%) was significantly higher than that in plasma (0.53%). The average pirazolac concentration in plasma within the dosing interval fluctuated between 30.9 micrograms/ml and 59 micrograms/ml, and in synovial fluid between 16.6 micrograms/ml and 29.9 micrograms/ml. The half-life of pirazolac calculated from the measured and interpolated data from all patients was 30.9 h in plasma and 66.2 h in synovial fluid. The absolute free concentrations in plasma and synovial fluid (approx. 250 ng/ml) were in the range of the IC50-values for inhibition of cyclooxygenase in mouse peritoneal macrophages.
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011720:Pyrazoles / Q000378:metabolism*; D012044:Regression Analysis; D013582:Synovial Fluid / Q000032:analysis*; D014018:Tissue Distribution
D001798:Blood Proteins; D011506:Proteins; D011720:Pyrazoles; C046317:pirazolac