Plasma concentration of phenylbutazone and its therapeutic effect-studies in patients with rheumatoid arthritis.

Abstract

1 Phenylbutazone in doses of 50, 100, 200 and 300 mg/day has been given for four periods of 3 weeks to seven patients with rheumatoid arthritis. The trial was double-blind and the order of administration of doses was arranged to eliminate order and carry-over effects. 2 Before the trial and at the end of each period, the patient's responses were assessed by measurement of the duration of morning stiffness, the pain score, paracetamol tablet count, grip strength, digital joint size and articular index. 3 The plasma phenybutazone concentration was measured by gas-liquid chromatography and was also predicted by prior measurement of the phenazone half-life. 4. Compared with the pretreatment period, phenylbutazone had a significant therapeutic effect, as judged by morning stiffness, pain score and articular index, in a dose of 50 mg/day, but no statistically significant differences in effect were seen between the various doses of phenylbutazone. 5 There were no significant coorelations between the plasma concentration of phenylbutazone and any of the clinical assessments. 6 The plasma phenylbutazone concentration agreed closely with that predicted at doses of 50 and 100 mg, but at higher doses the plasma concentration was significantly lower than predicted (P less than 0.05). This may have been due to saturation of the protein binding sites at these doses.