[Pharmacokinetic mechanisms of resistance to anticancer medications].
Besides the cellular mechanisms of resistance, which can be described in terms of molecular alterations, the lack of sensitivity of a tumour to a drug may result from an inadequacy between the pharmacokinetics of the drug and the kinetics of the tumour cells. Dose and duration of infusion of a drug may govern its activity; the drugs exhibiting a short half-life in plasma and a marked phase-dependence in their mechanism of action have to be administered as continuous infusions. The existence of sanctuary compartments within the body, which are protected by barriers such as the blood-brain barrier, may also contribute to the failure of the molecules unable to cross these barriers. Finally, the tumour cell kinetics may unfavour the general activity of drugs: this is the case of slowly growing tumours, which contain an important proportion of GO cells. The optimisation of the mode of administration of a drug is a requisite for the expression of its activity.
Robert
J
J
Fondation Bergonié, service de biochimie, Bordeaux, France.
D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D015251:Epirubicin / Q000008:administration & dosage; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D015251:Epirubicin; D005472:Fluorouracil
Les mécanismes pharmacocinétiques de résistance aux médicaments anticancéreux.