Comparison of linear and tapered intravenous infusion of methotrexate in oncochemotherapy. A theoretical approach
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In oncochemotherapy with methotrexate (MTX) a peripheral concentration >0.45 mg/l and a plasma concentration <45 mg/l must be maintained for 20 h. The time periods required to reach and maintain steady-state concentrations after tapered and linear intravenous infusion were compared. Pharmacokinetic analyses according to a two-compartment model were used to calculate dosage regimens and concentration profiles by means of the Bayesian General Modelling Program (BM) and NONLIN. When the dosage regimen is based on a steady-state concentration in the peripheral compartment (which is the target compartment for MTX) tapered infusion reaches this concentration 40% faster and maintains it 12.5% longer, but no difference is found if the dosage regimen is based on a steady-state concentration in the central compartment. In theory the two-step 24-hour tapered infusion can be replaced by a bolus injection plus linear infusion in the ratio 1∶2 of the total dose. These dosage regimens are to be preferred over linear infusion.
KeywordsMethotrexate Total Dose Concentration Profile Dosage Regimen Theoretical Approach
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- 2.Lankelma J, Van der Kleijn E, Termond EFS. Assay of Methotrexate and 7-Hydroxymethotrexate by high pressure liquid chromatography and its application to clinical pharmacokinetics. In: Pinedo HM, ed. Clinical Pharmacology of Anti-Neoplastic Agents. Amsterdam: Elsevier/North-Holland Biomedical Press, 1978:13–28.Google Scholar
- 3.Lippens RJJ. Methotrexate in the Central Nervous System Prophylaxis of Children with Acute Lymphoblastic Leukemia. Nijmegen: Catholic University of Nijmegen, 1981. Dissertation.Google Scholar
- 5.Metzler CM, Elfring GL, McEwen AJ. A Package of Computer Programs for Pharmacokinetic Modeling. Biometrics 1974;30:562.Google Scholar
- 7.Forest A, Gilman T, Rodman J, Jelliffe RW. A timeshared computer program for adaptive control of aminoglycoside therapy. Abstracts of the 8 1st annual meeting of the American Society for Clinical Pharmacology and Therapeutics, San Francisco, March 19–21, 1980. Clin Pharmacol Ther 1980;27:254.Google Scholar