LACK OF INTERACTION BETWEEN FLUCLOXACILLIN AND METHOTREXATE IN PATIENTS WITH RHEUMATOID-ARTHRITIS

1 The aim of the study was to examine the potential pharmacokinetic in teraction between methotrexate and flucloxacillin. 2 Ten rheumatoid ar thritis patients participated in the interaction study. Subjects were allocated to either methotrexate alone (5-15 mg per week) or methotrex ate plus flucloxacillin (500 mg four times a day 48 h prior to samplin g) in a random order. 3 There was a statistically, but not clinically, significant decrease in methotrexate AUC (1307+/-389 vs 1212+/-394 mu g l(-1) h) in the presence of flucloxacillin. C-max and t(max) parame ters for methotrexate were not significantly altered in the presence o f flucloxacillin. 4 Data from an additional 10 rheumatoid arthritis pa tients, starting on methotrexate, were added to the data from the plac ebo arm of the interaction study and a model dependent pharmacokinetic analysis was performed. The plasma concentration profiles were best d escribed by a two-compartment model with a mean clearance of 11.9 (+/- 1.7) 1 h(-1) and an initial volume of distribution of 31.2 (+/-2.6) 1, The pronounced intersubject variability in the pharmacokinetic parame ters was not related to any of the available covariate information. 5 Our findings suggest that no important clinical interaction occurs bet ween flucloxacillin and methotrexate in patients with rheumatoid arthr itis.