Disposition and clinical efficacy of methotrexate in patients with rheumatoid arthritis following weekly, low, intramuscular dosing: A pilot study

Sixteen patients with rheumatoid arthritis (RA) (2 men and 14 women; age, 17 to 57 years; body weight; 40 to 80 kg) were administered methotrexate (MTX) as an intramuscular (IM) injection in a dose regimen of 10 mg once weekly for at least 6 weeks. In the first nine patients, plasma concentrations of MTX were monitored for 96 hours following the last IM dosing with the drug. However, unmeasurable (<0.02 μmol/L) drug levels were observed 8 hours after drug administration. Therefore, in the remaining seven patients, MTX plasma levels were assessed for only 8 hours following drug administration. However, peak concentrations (C(max)) of the drug (mean ± SEM, 0.71 ± 0.10 pmol/L) were achieved in all patients 15 minutes after an IM injection of MTX. Total body clearance and apparent volume of distribution of MTX averaged 156.6 ± 18.9 mL/min and 0.64 ± 0.1 L/kg, respectively. The elimination half-life was 3.0 ± 0.27 hours. Clinical assessment of the patients showed less pronounced morning stiffness, improved functional capacity, and a significant reduction in the number of swollen and tender joints and in the value of erythrocyte sedimentation rate. Neither C,, nor area under the curve of achieved MTX plasma concentrations showed a significant correlation to the clinical efficacy of the drug. Nausea was the chief complaint of patients (n = 13) on this dosage regimen of MTX. In conclusion, MTX (10 mg/wk IM) is beneficial in the treatment of BA. However, pharmacokinetic evaluation of serum levels of MTX after once-weekly, 10-mg IM injections of the drug revealed no correlation between the serum level of MTX and its reputative efficacy in RA.