Cyclosporine A pharmacokinetics in rheumatoid arthritis patients after 6 months of methotrexate therapy

To evaluate the effects of a 6-month methotrexate (MTX) treatment period on cyclosporine A (CsA) pharmacokinetics were subsequently added in patients with rheumatoid arthritis (RA) in comparison with patients treated with CsA only, CsA was administered to 30 subjects with RA (group A) treated with M TX (10 mg week(-1) i.m.) for 6 months and to 30 patients (group B) who rece ived no MTX treatment. The mean doses +/- SD of CsA used in groups A and B were 3.2 +/- 0.5 and 3.3 +/- 0.4 mg kg(-1), respectively. CsA levels were d etermined in whole blood by means of a fluorescence polarization immunoassa y (FPIA) method with a specific monoclonal antibody. The following pharmaco kinetics parameters were calculated: area under the curve from 0 to 24 h (A UC(0-24)), half-life of the elimination phase (T-1/2 beta), total body clea rance CL . F-1; V . F-1 and apparent volume of distribution (V-d beta). The mean blood concentrations and the pharmacokinetic parameters calculated in group A did not present significant statistical differences in comparison to group B. In conclusion, a 6-month MTX therapy does not produce liver fun ction modifications to such an extent as to modify the pharmacokinetics of CsA subsequently added. Therefore, from a clinical pharmacological point of view, an MTX-CsA cotreatment appears feasible. (C) 1999 Academic Press.