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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