Cyclosporine a Pharmacokinetics in Rheumatoid Arthritis Patients After 6 Months of Methotrexate Therapy

Author： Baraldo M. Ferraccioli G. Pea F. Gremese E. Furlanut M.

ISSN： 1043-6618

Source： Pharmacological Research, Vol.40, Iss.6, 1999-12, pp. : 483-486

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Abstract

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 MTX (10 mg week^-1i.m.) for 6 months and to 30 patients (group B) who received 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 determined in whole blood by means of a fluorescence polarization immunoassay (FPIA) method with a specific monoclonal antibody. The following pharmacokinetics parameters were calculated: area under the curve from 0 to 24 h (AUC_0–24), half-life of the elimination phase (T_1/2&bgr;), total body clearance CL·F^-1; V·F^-1and apparent volume of distribution (V_d&bgr;). 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 function 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.pc 1999 Academic Press@p$hr