Pharmacokinetics of fenclofenac in children with juvenile rheumatoid arthritis

Summary Twenty eight children (age range 3–17 years) with juvenile rheumatoid arthritis (JRA) received fenclofenac 10–25 mg/kg body weight daily on an open basis. Pharmacokinetic analysis was undertaken on plasma fenclofenac levels measured during the first 3 weeks of treatment. The peak concentration after the first dose was achieved in 2–8 h in non-fasting subjects and was linearly related to dose. The plasma level then decayed biexponentially, as in adults, the initial distribution phase extending to about 12 h after dosing. After treatment for 18 days, blood samples were taken during the 96 h following the last dose of the drug to define the steady state elimination profile. The elimination half-life was 25.4±7.9 h (n=17) and did not appear to be dependent on the daily dosage. A therapeutic drug concentration of =100 µg/ml emerged from subjective and objective estimates of the response to treatment and measurement of steady state fenclofenac concentration. Treatment response could be more accurately predicted with the aid of drug concentrations than from dosage alone, although the dose and the steady state drug concentration were positively and linearly correlated (r=0.61,p<0.01). Of 16 children receiving doses in excess of 20 mg/kg/day, 3 experienced dose-related adverse effects, increased serum transaminase activity, vertigo and dyspnoea.