The intent of a prospective 3-month study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of low-dose methotrexate (LDMTX) in recalcitrant psoriasis en plaques. 15 males and 9 females (age 31-73 years) were assigned to 2 regimens of either 2.5-2.5-2.5 mg or 5-5-5 mg oral methotrexate (MTX), given in two 12-h intervals a week. HPLC was used to analysis of MTX concentrations in plasma and urine. The comparison of MTX minimum plasma concentrations revealed that the steady state is reached after a third subdose (p<0.01; Tukey HSD). Therefore, the body exposure to MTX was evaluated using the area under the curve of MTX plazma concentrations 24-36 h after the beginning of pharmacotherapy (AUC24-36hMTX). The total clearance ofMTX(CLtotMTX) ranged from 9.25 to 12.19 l/h and was proportional to the clearance of creatinine (CLCR) (r2=0.45; p<0.001). The renal clearance of the drug (CLrenMTX) corresponded to theCLCR (r2=0.41; p<0.001).CLCR correlated toAUC24-36hMTX (rs=-0.59; p<0.01). The effect ofLDMTXintermittent therapy was evaluated according to the PASI-score system. Analysis of regression revealed a highly significant inverse relationship between the final PASI-score (in percent of the initial status) and the steady-state AUC24-36hMTX at the beginning of the therapy (rs=-0.65, p<0.001). The steady-state AUCMTX >700 nmol.h/l is associated with a significantly better succes of antipsoriatic therapy when using oral LDMTX intermittent administration of 3 divided doses in two 12-h intervals.

        Key words: low-dose methotrexate - psoriasis - PASI score