Transsynovial distribution and protein binding of pirazolac in patients with rheumatoid arthritis

Abstract

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.

Recent Findings on the Pharmacokinetics of Non-Steroidal Anti-Inflammatory Drugs in Synovial Fluid

“…Abbreviations: A = single dose regimen; B = multiple-dose regimen; tmax = time to Cmax; Cmax = peak drug concentration; tv, = elimination half-life; ET = equilibrium time; SF = synovial fluid; P = plasma (or serum); (S) = S-enantiomer; (R) = R-enantiomer; OA = osteoarthritis; RA = rheumatoid arthritis; AUC SF/AUC P = ratio of synovial fluid to plasma (or serum) area under the curve; SF /P = ratio of synovial fluid to plasma (or serum) concentrations.References 1 Bannwarth et al (1985); 2 Sitar et al (1985); 3 Jalava et al (1983); 4 Chiccarelli et al (1980); 5 Aarons et al (1986); 6 Day et al (1988); 7 Gallo et al (1986); 8 McCrea et al (1986); 9 Netter et al (1987a); 10 Katona et al (1980); 11 Dougados et al (1986); 12 Bruno et al (1988); 13 Schoeller et al (1983); 14 Daymond & Herbert (1982); 15 Daymond & Herbert (1983);16 Nichol et al (1988); 17Kraml et al (1988);18 Fowler & Dawes (1985); 19Dromgoole et al (1982);20 Franchimont et al (1982);21 Mayrhofer & Thumb (1984); 22Kamp et al (1984);23 Farr et al (1982); 24Kurowski et al (1986); 25Kurowski et al (1987); 26Gaucher et al (1983b); 27Benson et al (1985);28 Fowler et al (1983); 29 Fowler et al (1986); 30Koup et al (1988); 31Ballerini et al (1985); 32Bannwarth et al (1986); 33 Strusberg et al (1983); 34 Thabe et al (1986); 35 Kurowski & Dunky (1988); 36 Cherie Ligniere et al (1987); 37 Bird et al (1985); 38 Hinderling et al (1988).…”

Studies on the reactions of cyclic oxalyl compounds with hydrazines or hydrazones : Synthesis and reactions of 4‐benzoyl‐1‐(3‐nitrophenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxylic acid

“…Pyrazole chemistry has been the focus of high attention for more than three decades due to versatile biological activities of pyrazole derivatives appearing as anti-microbial [1], anti-viral [2], anti-tumor [3], anti-inflammatory [4], anti-histaminic [5] pesticidal [6], anti-fungal [7], against rheumatoid arthritis [8], anti-convulsant [9], antidepressant [10] and anti-pyretic [11] agents. Our studies related to preparing pyrazole and fused pyrazole derivatives by the functionalization and cyclization reactions of 4 -b e n z o y l -1 , 5 -d i p h e n y l -1H-pyrazole-3-carboxylic acid with various nucleophiles was previously reported [12,13].…”

Biopolyphenolics as antioxidants: Studies under an Indo-Italian CSIR-CNR project

“…Owing to the widespread uses of pyrazole derivatives in medicine [31][32][33][34][35][36][37] and other areas of human activity [38][39][40][41][42][43][44], we have synthesized and evaluated the antioxidant activities of a large number of pyrazoles and their derivatives [45]. These include novel classes of heterocyclic compounds, i.e., pyranones (lactones) 16, 5-aryl-pyrazoles 17, 1,3-diarylpyrazoles 20, and acrylonitriles 18, 19, and 21.…”