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Pharmacokinetics Of Low-Dose Methotrexate Correlated With Antipsoriatic Effect
A DGReview of :"Pharmacokinetics and pharmacodynamics of low-dose methotrexate in the treatment of psoriasis."
British Journal of Clinical Pharmacology
09/10/2002
By James Adams
Pharmacokinetics and antipsoriatic effect of low-dose intermittent methotrexate are strongly correlated.
There is also significant interindividual variability in methotrexate pharmacokinetics, suggesting the importance of therapeutic monitoring and dose individuation at the beginning of therapy, according to investigators.
The investigators, from the Department of Pharmacology at Charles University and the Department of Dermatology at the University Hospital in Hradec Kralove, Czech Republic, studied 24 patients with psoriasis.
Patients received either 7.5 or 15 milligrams of methotrexate weekly. Each weekly dose was divided into three aliquots that were administered at 12-hour intervals.
The Psoriasis Area and Severity Index was used to assess skin impairment at baseline, and after five, nine and 13 weeks of treatment. Methotrexate pharmacokinetics were evaluated at week one and at week 13.
A 12 percent accumulation of methotrexate in the plasma was determined by comparing the areas under the plasma concentration time curve (AUCMTX) after the first and third weekly doses.
Interindividual variability in the AUCMTX was four times greater than intraindividual variability.
Eight patients from the 7.5-milligram group and nine patients from the 15-milligram group were classified as responders with a 50 percent decrease in scores on the Psoriasis Area and Severity Index.
A steady state AUCMTX value of 700 nanomoles l/l hour or higher was found to be associated with a significantly higher success rate in treating psoriasis. Thirteen of the 14 patients with steady state values greater than or equal to this number responded to therapy. Only four out of the remaining 10 patients with lower steady state values were responders.
Br J Clin Pharmacol 2002; 54(2): 147-156
"Pharmacokinetics and pharmacodynamics of low-dose methotrexate in the treatment of psoriasis."
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