Pharmacokinetic Study on One Case of High Dose Methotrexate Therapy with Leucovorin Rescue

High-dose methotrexate therapy in a testicular was studied pharmacokinetically to obtain safe and effective massive methotrexate theraphy. The drug concentration in serum, cerebrospinal fluid and urinary excretion was analyzed according to two-or three-compartment open models. The ratio of exposure to methotrexate in the central vs. the peripheral compartments was calculated to be 1 : 0.14 by a two-compartment open model. A larger amount of methotrexate permeates into the peripheral compartment by passive transport when a high dose, as compared to the usual dose, is used. However, most of the administered mothotrexate is rapidly excreted in urine without any antitumor effects, The urinary excretion showed almost the same pharmacokinetical parameters as obtained from the serum data. The analysis based on a three-compartment open model indicates that the low and sustained serum concentration of methotrexate at the third phase was found to be governed by its release from the third compartment. General consideration about cancer chemotherapy using methotrexate are also discussed.

Methotrexate

Pharmacokinetics

Cancer chemotherapy

High dose methotrexate therapy