Are there differences in methotrexate kinetics between responding and nonresponding patients with rheumatoid arthritis?
OBJECTIVE
The purpose of this study was to investigate the presence of a correlation between methotrexate pharmacokinetics and clinical efficacy in patients with rheumatoid arthritis.


METHODS
The study was carried out in 29 patients with rheumatoid arthritis. The patients received intramuscular methotrexate (MTX) 7.5mg once a week for 8 weeks. Before and 0.5, 1, 2, 3, 4, 6, 9, 12 and 24 hours after the first administration, MTX serum concentrations were measured and pharmacokinetic investigations were carried out. The clinical status of the disease was evaluated before and after 8 weeks of therapy. In addition, before and after 2 and 8 weeks of treatment, the patients were monitored for a complete biochemical profile. After 8 weeks of treatment, on the basis of improvement in clinical parameters, the patients were designated responders or nonresponders.


RESULTS
A clinical response was obtained in 62% of patients (18 patients responded and 11 did not) and was associated with a low incidence of adverse effects. There were no differences in the pharmacokinetic parameters of MTX between the 2 groups of patients (responders vs nonresponders), except that t(max) was significantly higher in nonresponders than in responders (p < 0.05).


CONCLUSIONS
These data confirm the efficacy and tolerability of low dose MTX in patients with rheumatoid arthritis in the short term, but appear to exclude a relationship between MTX kinetics and clinical response.
Department of Neurosciences, Section of Pharmacology, School of Medicine, Federico II University, Naples, Italy. domenicocapone@hotmail.com
D
D
Capone
A
A
Spanò
A
A
Gentile
G
G
Ferrara
E
E
Itto
G
G
Palmiero
V
V
Basile
P
P
Oriente