Monitoring methotrexate therapy in patients with rheumatoid arthritis.
OBJECTIVE
The aim of this work was to study methotrexate (MTX) kinetics and their relation to the effectiveness of the therapy in patients with rheumatoid arthritis (RA). Other aims were to analyze the influence of MTX on liver, kidney, hematopoietic function and to determine the possibility of using early drug concentrations to predict the subsequent value of the treatment.


METHODS
The observations were carried out in 49 patients with RA after the first dose of MTX and after 7 months of treatment. Methotrexate concentrations in blood serum and urine were determined using fluorescence polarization immunoassay applying a TDx Abbott analyzer.


RESULTS
No correlation between concentrations, pharmacokinetic parameters and the duration of the disease, its activity, clinical symptoms, observations pertaining to the disease made by physician and patients and morning stiffness of joints was seen. Of those tests for the evaluation of liver, kidney and hematopoietic function, only the mean activity of N-acetyl-beta-D-glucosaminidase (NAG) in urine was significantly elevated both before and after treatment with MTX when compared to corresponding values in the control group of healthy subjects. We have formulated equations allowing for the early recognition of patients with a risk of adverse effects due to impaired elimination of MTX from the body.


CONCLUSIONS
Our results show that monitoring MTX therapy using concentrations in patients with RA does not significantly improve the effectiveness of the treatment, but it can play an important role in increasing the safety of this drug.
Wiela-Hojenska
A
A
Department of Clinical Pharmacology, Wroclaw Medical University, Wroclaw, Poland. wiela@farmklin.am.wroc.pl
Orzechowska-Juzwenko
K
K
Swierkot
J
J
Wiland
P
P
Hurkacz
M
M
Szechinski
J
J
D018501:Antirheumatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D006207:Half-Life; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008727:Methotrexate / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008727:Methotrexate