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Lack of interaction between flucloxacillin and methotrexate in pa tien t s with rheumatoid arthritis
Author(s) -
HERRICK ARIANE L.,
GRENNAN DAVID M.,
GRIFFEN KERRY,
AARONS LEON,
GIFFORD LARRY A.
Publication year - 1996
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1996.tb00186.x
Subject(s) - flucloxacillin , rheumatoid arthritis , methotrexate , pharmacokinetics , medicine , pharmacology , arthritis , volume of distribution , placebo , drug interaction , gastroenterology , pathology , alternative medicine , biology , bacteria , genetics , staphylococcus aureus
1 The aim of the study was to examine the potential pharmacokinetic interaction between methotrexate and flucloxacillin. 2 Ten rheumatoid arthritis patients participated in the interaction study. Subjects were allocated to either methotrexate alone (5–15 mg per week) or methotrexate plus flucloxacillin (500 mg four times a day 48 h prior to sampling) in a random order. 3 There was a statistically, but not clinically, significant decrease in methotrexate AUC (1307 ± 389 vs 1212 ± 394 μg 1‐ ‐1 h) in the presence of flucloxacillin. C max and t max parameters for methotrexate were not significantly altered in the presence of flucloxacillin. 4 Data from an additional 10 rheumatoid arthritis patients, starting on methotrexate, were added to the data from the placebo arm of the interaction study and a model dependent pharmacokinetic analysis was performed. The plasma concentration profiles were best described 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 parameters was not related to any of the available covariate information. 5 Our findings suggest that no important clinical interaction occurs between flucloxacillin and methotrexate in patients with rheumatoid arthritis.