Advantages and limitations of pharmacokinetic studies in the rationalization of anticancer therapy: methotrexate and 5-FU.
The use of pharmacokinetic studies for individual dose regimen adjustments in anticancer therapy is considered. The example of methotrexate in the treatment of head and neck tumors demonstrates the validity of this approach. Moreover, the importance of biotransformations of this antimetabolite is confirmed using a high pressure liquid chromatography assay. The example of 5-FU outlines the analytical and mathematical difficulties rendering this approach unlikely for routine use. Some preliminary relations between pharmacokinetic parameters (plasma clearance) and clinical response are presented. The determination of the main plasma metabolic 5-6 dihydro 5-FU by GC/MS and its possible role in the nonlinear pharmacokinetics of the drug in therapeutic failure are discussed.
D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008727:Methotrexate / Q000008:administration & dosage / Q000378:metabolism*; D008954:Models, Biological
C019389:5-fluorodihydrouracil; D005472:Fluorouracil; D008727:Methotrexate