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Pharmacokinetics of fenclofenac in children with juvenile rheumatoid arthritis
Insights
Fenclofenac treatment in children with juvenile rheumatoid arthritis (JRA) shows that drug concentration, not just dosage, predicts treatment response. Therapeutic levels of 100 micrograms/ml are achievable, but higher doses may cause adverse effects.
Area of Science:
- Pediatric Rheumatology
- Pharmacokinetics
- Drug Metabolism
Background:
- Juvenile rheumatoid arthritis (JRA) is a chronic inflammatory condition affecting children.
- Fenclofenac is a non-steroidal anti-inflammatory drug (NSAID) used to manage JRA symptoms.
- Understanding fenclofenac pharmacokinetics in children is crucial for optimizing treatment and minimizing adverse effects.
Purpose of the Study:
- To evaluate the pharmacokinetics of fenclofenac in children with JRA.
- To determine the relationship between fenclofenac dosage, plasma concentration, and therapeutic response.
- To identify potential adverse effects associated with fenclofenac treatment in pediatric patients.
Main Methods:
- Open-label study involving 28 children (3-17 years) with JRA receiving fenclofenac (10-25 mg/kg/day).
- Plasma fenclofenac levels were measured during the first 3 weeks of treatment.
- Pharmacokinetic analysis included peak concentration, distribution, elimination half-life, and steady-state levels.
Main Results:
- Peak plasma fenclofenac concentration was dose-dependent and achieved within 2-8 hours.
- The elimination half-life was approximately 25.4 +/- 7.9 hours.
- A therapeutic drug concentration (≥100 µg/ml) correlated with treatment response, outperforming dosage alone.
- Higher doses (>20 mg/kg/day) were associated with dose-related adverse effects in 3 of 16 children.
Conclusions:
- Fenclofenac pharmacokinetics in children with JRA are similar to adults.
- Monitoring plasma fenclofenac concentrations aids in predicting therapeutic response and optimizing dosage.
- Careful dose titration is recommended to balance efficacy and minimize adverse events in pediatric patients.
Abstract:
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 greater than or equal to 100 micrograms/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 less than 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.