[Pharmacokinetic-pharmacodynamics relationships of imatinib (Glivec)].
Imatinib (Glivec) is a specific inhibitor of tyrosine kinase receptor, in particular of the proto-oncogene c-kit. Proto-oncogene c-kit is expressed or mutated in stromal digestive tumors (GIST). Pharmacokinetic (PK) analysis showed that imatinib displayed linear PK in patients with advanced GIST. Imatinib is extensively metabolized by the cytochrome P450 enzyme system. Alpha-1-acid glycoprotein (AAG), a protein involved in the acute phase of inflammation, is implicated in protein binding of imatinib and seems to play a key role in imatinib PK.
Delbaldo
Catherine
C
Service d'oncologie, Hôpital Henri-Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, France. catherine.delbaldo@hmn.aphp.fr
D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004361:Drug Tolerance; D006801:Humans; D000068877:Imatinib Mesylate; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; C000715470:MAS1 protein, human; D010879:Piperazines; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D003577:Cytochrome P-450 Enzyme System