TOTAL AND FREE METHOTREXATE PHARMACOKINETICS, WITH AND WITHOUT PIROXICAM, IN RHEUMATOID-ARTHRITIS PATIENTS

The pharmacokinetic profile of total and free methotrexate (MTX) and t he effect of piroxicam on MTX pharmacokinetics was studied in 20 rheum atoid arthritis patients receiving a stable dosage of MTX (10 mg/week) . Plasma protein binding ranged from 25 to 55%. To describe the variat ions with time of the unbound fractions a mathematical characterizatio n relationship between the total and free MTX was used. Total and free MTX were correlated with the sigmoid maximum effect model. The slope factor (gamma) was proportional to the number of binding sites. The fr ee fraction for a given patient can be evaluated from this relationshi p. Total clearance of MTX was not statistically different with piroxic am (8.01/h for total MTX, 13.71/h for free MTX) vs without piroxicam. Likewise, there were no significant difference in t(max), area under t he plasma concentration vs time curve, distribution and elimination ha lf-lives, mean resonance time, and volumes of distribution. Although t he highest observed total MTX concentration was significantly lower wi th piroxicam, there were no significant pharmacokinetic interactions b etween low-dose MTX and piroxicam.