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; a ge, 17 to 57 years; body weight, 40 to 80 kg) were administered methot rexate (MTX) as an intramuscular (IM) injection in a dose regimen of 1 0 mg once weekly for at least 6 weeks. In the first nine patients, pla sma concentrations of MTX were monitored for 96 hours following the la st IM dosing with the drug. However, unmeasurable (<0.02 mu mol/L) dru g levels were observed 8 hours after drug administration. Therefore, i n the remaining seven patients, MTX plasma levels were assessed for on ly 8 hours following drug administration. However, peak concentrations (C-max) of the drug (mean +/- SEM, 0.71 +/- 0.10 mu mol/L) were achie ved in all patients 15 minutes after an IM injection of MTX. Total bod y 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 h alf-life was 3.0 +/- 0.27 hours. Clinical assessment of the patients s howed less pronounced morning stiffness, improved functional capacity, and a significant reduction in the number of swollen and tender joint s and in the value of erythrocyte sedimentation rate. Neither C,, nor area under the curve of achieved MTX plasma concentrations showed a si gnificant correlation to the clinical efficacy of the drug. Nausea was the chief complaint of patients (n = 13) on this dosage regimen of MT X. In conclusion, MTX (10 mg/wk IM) is beneficial in the treatment of RA. However, pharmacokinetic evaluation of serum levels of MTX after o nce-weekly, 10-mg IM injections of the drug revealed no correlation be tween the serum level of MTX and its reputative efficacy in RA.