Ibuprofen Levels in Serum and Synovial Fluid

Abstract

Ibuprofen levels were measured in the serum and synovial fluid of 33 children (mean age 11 years) with juvenile chronic arthritis. A total daily dose of about 40 mg of ibuprofen per kg of body weight (mean 37.1 mg/kg) was given in three portions. In serum the peak level was reached 1-2 hours after drug intake. The half-life of elimination in swum WPP 2.3k0.5 hours (mean k 1 S.D., n=12). Twelve hours after the last dose the mean serum level was about 20 jmol/l. Ibuprofen concentrations fluctuated far less In synovial M d than in serum. In synovlal fluid peak levels (mean 65 pmd/l) were reached 5-6 hwrs after drug intake. Thereafter, the levels declined slowly but 12 h w r s later were still higher than In serum.

Ibuprofen: pharmacology, efficacy and safety

“…3). The absorption of oral ibuprofen is rapid and comparable to that in adults (Mäkelä et al 1979(Mäkelä et al , 1981. In 33 patients (1.5-15 years) that received approximately 40 mg kg -1 day -1 t.i.d., peak serum concentrations C max were 31 lg mL -1 at 1.0-2.0 h. The t 1/2 was 2.3 h which is comparable with that in adults.…”

“…Stereospecific disposition of ibuprofen enantiomers occurs into the synovial fluids of arthritic patients, many of whom have synovitis or inflammation of their knees. There is appreciable accumulation of R/S-ibuprofen in synovial fluids with broad peaks occurring over a period of 2-6 h which follows the peak plasma or serum concentrations (Glass and Swannell 1978;Mäkelä et al 1981;Albert and Gernaat 1984;Gallo et al 1986). The ratios of total ibuprofen concentrations in the synovial fluid to those in plasma is about 1.24 at 7 h following single dose of 600 mg of the drug and 0.52-1.46 at 3-12 h after 3 daily doses of ibuprofen 1.8 g day -1 (Gallo et al 1986).…”

“…Among the earlier published reports of the PK of ibuprofen in juvenile arthritis were two studies by Mäkelä et al (1979Mäkelä et al ( , 1981. These authors determined the concentrations of racemic drug in serum and synovial fluids in 17 patients with juvenile arthritis (aged 1.5-15 years) who received approximately 40 mg kg -1 day -1 ibuprofen.…”

Treatment of juvenile rheumatoid arthritis

“…The suspension that is commonly administered to children consists of both S and R enantiomers and is not absorbed as well as the tablets6). It should therefore be given at a dosage of approximately 45 mg kg -1 d -1 divided into 3 or 4 doses.…”

“…The costimulation modifier abatacept was also shown to be effective and relatively well tolerated according to a short-term analysis of patients, which also resulted in FDA approval. Continued FDA procedures for monitoring safety will improve the ability to identify short- and long-term toxicities of these new agents6).…”