Methotrexate. II. Use in pediatric chemotherapy.
The comprehensive use of methotrexate is possible because there is an easy way of reducing the toxic effects of this drug. Effective in the antidotic action are alkalinization of the urine, increasing hydration of the patient, and "rescue" of purine and pyrimidine metabolism in the tissues by use of reduced folates. Only intravenous administration, by means of infusion given over a long period (24 hours or more), results in reliable and reproducible concentrations in the plasma. Oral administration should be abandoned because of the variable resorption and the different concentrations reached in plasma by different individuals. Local administration, such as by intrathecal injection, is useful only when the interval between two succeeding injections is 14 days or more. On the basis of known pharmacokinetic constants, the dose of methotrexate and of citrovorum factor (leucovorin) which will result in the desired concentration in plasma, and possibly also in tissues, can easily be calculated. Use of the principle of concentration X time in dosage calculations will result in the avoidance of giving unnecessarily high doses of methotrexate.
D000284:Administration, Oral; D002490:Central Nervous System / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000188:drug therapy; D002648:Child; D004247:DNA / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D006801:Humans; D007263:Infusions, Parenteral; D007278:Injections, Spinal; D007700:Kinetics; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D007938:Leukemia / Q000188:drug therapy; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000134:cerebrospinal fluid / Q000627:therapeutic use
D004247:DNA; D002955:Leucovorin; D008727:Methotrexate