Erlotinib is a synthetic anilinoquinazoline compound that selectively binds to the ATP-binding site of the epidermal growth factor receptor (EGFR)-TK, which inhibits receptor tyrosine kinases (TKs) by inhibition of the intercellular domain (PMID: 14676101; PMID: 15217965). Erlotinib also inhibits ATP-binding cassette transporter-mediated drug efflux, which in turn strongly increases the intracellular concentrations of co-administrated drug molecules that are transporter substrates. Erlotinib is given orally to adults with advanced stages of certain carcinomas, with diarrhea and rash as known adverse reactions.
After oral administration, erlotinib is widely distributed throughout the body. Erlotinib is metabolized in the liver by cytochrome P450s, primarily by CYP3A4 and CYP1A1, but CYP3A5 also plays a minor role in erlotinib metabolism. In addition to its role as an ABC transporter inhibitor, erlotinib has also been implicated as an inhibitor of CYP2C8 and UGT1A1 activity. Therefore, erlotinib may inhibit the metabolism of co-administered drugs that are substrates of CYP2C8 and UGT1A1.
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
Entities in the Pathway
Drugs/Drug Classes (1)
Relationships in the Pathway
|Arrow From||Arrow To||Controllers||PMID|
|erlotinib||OSI 420||CYP1A1, CYP1A2, CYP3A4, CYP3A5||11432895, 16166415, 16381666, 16490804, 16890575, 17575239, 19733976|
|erlotinib||erlotinib||ABCB1, ABCG2||15155841, 15492275, 16651435, 17312388|
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