Pharmacokinetics of methotrexate in erythrocytes in psoriasis.

The intraerythrocytic levels of folate and methotrexate were measured in 25 patients on long-term methotrexate therapy for recalcitrant psoriasis. The mean steady state concentration of methotrexate in erythrocytes was 85 nmol/l and the mean erythrocyte folate concentration was 729 nmol/l. A linear correlation was not observed between these parameters, but the greatest methotrexate accumulation was found in cells at the lower end of the erythrocyte folate concentration range. In 5 patients started on methotrexate therapy the erythrocyte concentrations of methotrexate and folate were followed over 6 months. 3-4 days after the first dose, methotrexate had been accumulated against a concentration gradient in the erythrocytes. The methotrexate concentration increased steadily until the steady state level was reached after 4-6 weeks. The steady state level was maintained during the 6 month observation period. The erythrocyte folate concentration did not change during this period. The data suggest that methotrexate polyglutamate synthesis within the circulating erythrocyte is a major cause of methotrexate accumulation in these cells.