Lack of correlation between pharmacokinetics and efficacy of low dose methotrexate in patients with rheumatoid arthritis.
OBJECTIVE
To determine if the variability in the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA) is correlated with its pharmacokinetics.


METHODS
MTX pharmacokinetics was evaluated in 46 patients with RA starting a weekly intramuscular low dose MTX treatment. The patients were divided into 32 responders and 14 nonresponders to MTX according to the clinical response in the 6 months after the pharmacokinetic study. MTX plasma (at T0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h) and urine concentrations were measured with the TDx Abbott fluorescence polarization immunoassay.


RESULTS
The MTX dosage, age, sex, RA duration, hepatic and renal functions of responders and nonresponders were not different. No difference was found either in peak concentration, residual 24th hour concentration, area under the curve, total body clearance, renal clearance, and terminal T1/2 life of MTX in responders and nonresponders. Surprisingly, patients with adverse reactions had higher total body and renal MTX clearances than those without side effects during the study.


CONCLUSIONS
These data suggest that plasma MTX measurements are not helpful in defining an optimal treatment regimen.
Lafforgue
P
P
Department of Rheumatology, Timone Hospital, Marseilles, France.
Monjanel-Mouterde
S
S
Durand
A
A
Catalin
J
J
Acquaviva
P C
PC
D000328:Adult; D017677:Age Distribution; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D017678:Sex Distribution; D013997:Time Factors
D018501:Antirheumatic Agents; D008727:Methotrexate