Disposition and clinical efficacy of methotrexate in patients with rheumatoid arthritis following weekly low intramuscular dosing

ABSTRACT

In sixteen patients with rheumatoid arthritis [RA], plasma concentrations of methotrexate [MTX] were monitored for 24 hours following the intramuscular [im] dosing with 10 mg per week for at least six weeks. Peak concentrations [0.7 +/- 0.5 mumol/l] were achieved 15 minutes following im injection of the drug, while immeasurable drug levels were observed after 24 hours following its injection. Total body clearance [CL/F] and apparent volume of distribution [V/F] averaged 157 ml/min and 0.64 L/kg, respectively. The elimination half-life was 3.0 +/- 1.1 hours. Clinical assessment of the patients showed less pronounced morning stiffness, improved functional capacity and significant reduction in both articular index score and joint swelling. Nausea was the most common side effect of MTX in this dosage regimen. It was concluded that MTX [10 mg im/week] possess a favorable benefit/risk ratio for the treatment of RA and in such patients the pharmacokinetic parameters are variable but comparable to literature data. There is no relation between the serum level of the drug and its efficacy in RA when administered once weekly