Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis

Area of Science:

• Pediatric Rheumatology
• Pharmacokinetics
• Drug Interactions

Background:

• Juvenile rheumatoid arthritis (JRA) is a chronic autoimmune disease affecting children.
• Management of JRA often involves nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX).
• Potential drug interactions between NSAIDs and MTX in pediatric populations require thorough investigation.

Purpose of the Study:

• To evaluate the pharmacokinetic interaction between naproxen and methotrexate in children diagnosed with JRA.
• To determine how co-administration of naproxen and MTX affects the kinetics of each drug in pediatric patients.

Main Methods:

• A pharmacokinetic study was conducted involving nine children with JRA.
• Each child served as their own control, receiving their established doses of MTX and naproxen individually and in combination.
• Drug levels and kinetic parameters were analyzed to assess interaction effects.

Main Results:

• Methotrexate significantly altered naproxen pharmacokinetics in 6 out of 8 patients (a change of >= 30%).
• Naproxen altered methotrexate pharmacokinetics in 4 out of 9 patients (a change of >= 30%).
• These findings indicate a bidirectional pharmacokinetic interaction between MTX and naproxen in JRA patients.

Conclusions:

• Methotrexate can influence the absorption and elimination of NSAIDs, such as naproxen, in children with JRA.
• Conversely, NSAIDs can also impact the pharmacokinetics of methotrexate.
• Close monitoring for adverse events is crucial when prescribing combination therapy of MTX and NSAIDs in pediatric patients to mitigate potential toxicity.