Simultaneous pharmacokinetics of indomethacin in serum and synovial fluid.

Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis [proceedings]

“…Up to 150 min after administration of the dose, the concentration of ibuprofen was higher in serum than in synovial fluid but thereafter a majority of the patients had a higher concentration of the drug in the synovial fluid. Thus the pharmacokinetics of ibuprofen in both fluids are qualitatively similar to those reported for acetylsalicylic acid (Sholkoff, Eyring, Rowland & Riegelman, 1967), alclofenac (Thomas, Dippy & Maddock, 1975), ketoprofen (Mitchell, Scott, Kennedy, Brooks, Templeton & Jefferies, 1975) and indomethacin (Emori, Champion, Bluestone & Paulus, 1973). They differ from those of total salicylate (Rosenthall, Bayles & Frement-Smith, 1964) and gold (Gerber, Paulus, Bluestone & Lederer, 1972) for which the drug concentration in synovial fluid was substantially lower than that in serum following equilibration.…”

The effect of non‐steroidal anti‐inflammatory drugs on the accumulation and release of interleukin‐1‐like activity by peritoneal macrophages from the mouse

“…Although the cyclo-oxygenaseindependent action of the NSAIDs on mouse macrophages occurs over higher concentration-ranges, these concentrations may well have some significance in vivo. In one study of arthritic patients, a single dose of 50mg of indomethacin produced a free plasma concentration of the drug of 1 to 8 pM (Emori et al, 1973). In another study, a dose of 25 mg of indomethacin gave plasma concentrations of 1.5 to 8.5 JiM (Hvidberg et al, 1972).…”

Prostaglandin Production by Macrophages and the Effect of Anti‐inflammatory Drugs

“…However, pharmacokinetic studies with indomethacin have shown that symptomatic relief (analgesia) of inflammatory joint disease in man is more closely associated with drug levels in synovial fluid than in blood (Emori, Champion, Bluestone & Paulus, 1973;Brooks, Bell, Lee, Rooney & Dick, 1974). Nonetheless the level of indomethacin attained in synovial fluid (approximately 0.7 jg/ml) following the oral administration of therapeutic dosage in man (Emori et al, 1973) is sufficient to inhibit by more than 90%, prostaglandin production by guinea-pig macrophages (Figure 2) even allowing for a high degree (95%) of protein binding.…”

“…However, pharmacokinetic studies with indomethacin have shown that symptomatic relief (analgesia) of inflammatory joint disease in man is more closely associated with drug levels in synovial fluid than in blood (Emori, Champion, Bluestone & Paulus, 1973;Brooks, Bell, Lee, Rooney & Dick, 1974). Nonetheless the level of indomethacin attained in synovial fluid (approximately 0.7 jg/ml) following the oral administration of therapeutic dosage in man (Emori et al, 1973) is sufficient to inhibit by more than 90%, prostaglandin production by guinea-pig macrophages (Figure 2) even allowing for a high degree (95%) of protein binding. Similarly, synovial free drug concentrations achieved following clinically active doses of three other drugs which have been studied, ketoprofen (Mitchell et al, 1975), feprazone (Cherie-Ligniere et al, 1974) and aspirin (Rosenthal et al, 1964;Sholkoff et al, 1967) are sufficient to inhibit macrophage prostaglandin synthesis to a comparable degree.…”