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Test dose for predicting high‐dose methotrexate infusions
Author(s) -
Kerr Ian G,
Jolivet Jacques,
Collins Jerry M,
Drake James C,
Chabner Bruce A
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.6
Subject(s) - methotrexate , bolus (digestion) , pharmacokinetics , medicine , pharmacology , plasma clearance , creatinine , renal function , clearance , maintenance dose , loading dose , urology , chemistry
Eighteen evaluable patients were studied to determine 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/m 2 ) was given to patients who were followed for 12 to 24 hr and the kinetic data were used to predict subsequent kinetic behavior of moderate‐ and high‐dose methotrexate infusions (150 to 1500 mg/m 2 over 12 to 18 hr). After test‐dose injection, MTX clearance varied from 36 to 138 ml/min/m 2 and decreased with advancing age (r = −0.49, P < 0.05). MTX clearance varied from 24 to 100 m /min/m 2 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/m 2 . 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‐hr (r = 0.92, P < 0.001) MTX concentrations after high‐dose infusions. Our results indicate that test‐dose MTX kinetics may serve as a guide to dose modification of MTX infusions in some high‐risk patients. Clinical Pharmacology and Therapeutics (1983) 33, 44–51; doi: 10.1038/clpt.1983.6