Ucinek a farmakokinetika nizkodavkovaneho metotrexatu v lecbe psoriazy.

Abstract

Two clinical studies with low-dose methotrexate (LDMTX) in the therapy of psoriasis were performed to answer if the relationship between the pharmacokinetics (PK) and pharmacodynamics (PD) exists and if it is possible to use results for the dose optimization in clinical practice. 11 patients were treated with 15 mg MTX and 7 patients with 7,5 mg MTX once a week. To perform a detailed evaluation of PK, plasma samples were drawn and urine was collected before and at the 13th week of the drug administration. The concentrations of MTX and its chief metabolite 7-OHMTX were determined by HPLC with UV detection. Maximum plasma concentration, time to reach a maximum plasma conc., the area under the plasma conc. time curve and renal clearance of MTX were measured and calculated. Similar PK was determined for 7-OHMTX. The data were used to correlate PK and PD. The efficacy of the therapy was evaluated by the PASI score. The score evaluates a clinical severity of psoriasis. At the end of the study the PASI score was calculated in percent of its initial value. MTX has the intracellular mechanism of action. Therefore, LDMTX efficacy and toxicity was evaluated in respect to MTX intracellular conc. in erythrocytes in steady state. The data were achieved by enzymatic spectrophotometry, evaluation of dihydrofolatereductase activity decrease in the presence of MTX. The study showed at least 4-times higher interindividual variability of PK parameters if compared to intraindividual var.. However, the therapy with 7,5 mg MTX was not very successful because of the low efficacy. Otherwise, the administration of 15 mg MTX as a bolus led to adverse effects (headache or nausea). Therefore, the next study was performed with LDMTX 7,5 and 15 mg a week divided into three aliquots given at 12-hour intervals. The divided dose schedule seems to be more convenient.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi