Are there differences in methotrexate kinetics between responding and nonresponding patients with rheumatoid arthritis?

Objective and Study Design: The purpose of this study was to investigate th e presence of a correlation between methotrexate pharmacokinetics and clini cal efficacy in patients with rheumatoid arthritis. Patients and Methods: The study was carried out in 29 patients with rheumat oid arthritis. The patients received intramuscular methotrexate (MTX) 7.5mg once a week for 8 weeks. Before and 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the first administration, MTX serum concentrations were measured and pharmacokinetic investigations were carried out. The clinical status of th e disease was evaluated before and after 8 weeks of therapy. In addition, b efore and after 2 and 8 weeks of treatment, the patients were monitored for a complete biochemical profile. After 8 weeks of treatment, on the basis o f improvement in clinical parameters, the patients were designated responde rs or nonresponders. Results: A clinical response was obtained in 62% of patients (18 patients r esponded and 11 did not) and was associated with a low incidence of adverse effects. There were no differences in the pharmacokinetic parameters of MT X between the 2 groups of patients (responders vs nonresponders), except th at t(max) was significantly higher in nonresponders than in responders (p < 0.05). Conclusions: These data confirm the efficacy and tolerability of low dose M TX in patients with rheumatoid arthritis in the short term, but appear to e xclude a relationship between MTX kinetics and clinical response.