The frequency of malignant neoplasms was studied in 248 psoriatics treated with a single, weekly, oral dose of methotrexate ranging from 5 to 25 mg. The follow-up period ranged from 5 to 14 years with a median of 7 years. The following 10 malignant neoplasms were found: ovarian cancer 3, breast cancer 2, esophageal cancer in 1 male, pancreatic cancer in 1 female, malignant lymphoma in 1 female and 1 male and 1 squamous cell carcinoma of the scrotal skin. As the observed number of malignant neoplasms was considerably smaller than the expected number, it is concluded that methotrexate therapy as used in the treatment of psoriasis does not seem to contribute to the development of malignant neoplasms.
The plasma concentration and urinary excretion of methotrexate were followed in twelve psoriatic patients after intravenous and oral doses of methotrexate ranging from 7.5 to 30 mg. In six of the patients, a nonlinear relation was found between the fractional amount of methotrexate excreted in the urine and the corresponding area under the plasma concentration-time curve. The methotrexate clearance was found to be increased during the initial high plasma concentration, probably due to saturation of the tubular reabsorption of methotrexate. Considerable interindividual variation was found in the apparent saturation point of the active reabsorption, but up to 500-800 ng/ml first order kinetics still applied. At plasma concentrations below saturation, the renal clearance of methotrexate ranged from 52-102 ml/min (mean +/- SD, 83 +/- 19.4 ml/min).
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