Comparison of linear and tapered intravenous infusion of methotrexate in oncochemotherapy. A theoretical approach.
In oncochemotherapy with methotrexate (MTX) a peripheral concentration greater than 0.45 mg/l and a plasma concentration less than 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.
D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy; D013223:Statistics as Topic
D008727:Methotrexate