Test dose for predicting high-dose methotrexate infusions

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Abstract
Evaluable patients (18) were studied to determne whether individual methotrexate (MTX) kinetics, determined by test-dose bolus injection, could be used to predict plasma drug concentrations during and after high-dose infusion. Small nontoxic doses of MTX (10 mg/m2) were given to patients [with non-Hodgkin''s lymphoma] who were followed for 12-24 h and the kinetic data were used to predict subsequent kinetic behavior of moderate- and high-dose MTX infusions (150-1500 mg/m2 over 12-18 h). After test-dose injection, MTX clearance varied from 36 to 138 ml/min per m2 and decreased with advancing age (r = -0.49, P < 0.05). MTX clearance varied from 24 to 100 ml/min per m2 after high-doses. Although there was a trend to decreasing clearance with advancing age, this was not as clear as with the test dose (r = -0.42, P > 0.05). There was no correlation between MTX clearance and creatinine clearance in this group of patients, in whom creatinine clearance varied from 32 to 63 ml/min per m2. When the kinetic parameters derived from the test-dose data were used, accurate predictions could be made of the infusion plateau (r = 0.89, P < 0.001) and 24-h (r = 0.92, P < 0.001) MTX concentrations after high-dose infusions. Test-dose MTX kinetics may serve as a guide to dose modification of MTX infusions in some high-risk patients.

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