title: Drug interaction between erlotinib and phenytoin for brain metastases in a patient with nonsmall cell lung cancer.
abstract: Erlotinib, a substrate drug metabolized by the CYP3A4 enzyme, is an epidermal growth factor receptor tyrosine kinase inhibitor used to treat nonsmall cell lung cancer (NSCLC). Concomitant use of erlotinib and the antiepileptic drug phenytoin, an inducer of CYP3A4, may result in a drug-drug interaction accompanied by changes in the blood concentrations of both drugs. We determined the blood concentration of each drug to confirm the interaction between phenytoin and erlotinib in a case of NSCLC with brain metastases. The phenytoin blood concentration (8.2-10.0μg/mL) gradually increased 3-fold (to 24.2μg/mL) 7 months after the start of erlotinib (150mg/d) co-administration. The erlotinib blood concentration which was maintained at 0.15-0.37μg/mL under phenytoin co-administration, increased 12-fold (to 1.77μg/mL) after the stoppage of phenytoin co-administration. The present case revealed that blood phenytoin increased and blood erlotinib decreased subsequent to the interaction of the 2 drugs in the CYP3A4 metabolic enzyme system.
authors: Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba,1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Department of Pharmacy, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama-shi, Ibaraki 309-1793, Japan. Electronic address: s1430453@u.tsukuba.ac.jp.
authors: Masahiro
authors: M
authors: Ohgami
authors: Department of Respiratory Medicine, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama-shi, Ibaraki, 309-1793, Japan. Electronic address: t-kaburagi@chubyoin.pref.ibaraki.jp.
authors: Takayuki
authors: T
authors: Kaburagi
authors: Department of Pharmacy, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama-shi, Ibaraki 309-1793, Japan. Electronic address: t-kurosawa@chubyoin.pref.ibaraki.jp.
authors: Atsuhiko
authors: A
authors: Kurosawa
authors: Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba,1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. Electronic address: masatoh@md.tsukuba.ac.jp.
authors: Masato
authors: M
authors: Homma
mesh_terms: D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D065694:Cytochrome P-450 CYP1A2 Inducers / Q000097:blood / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D065694:Cytochrome P-450 CYP1A2 Inducers; D047428:Protein Kinase Inhibitors; D010672:Phenytoin; D000069347:Erlotinib Hydrochloride; D051544:Cytochrome P-450 CYP3A; D066246:ErbB Receptors
keywords: Drug-drug interaction; Erlotinib; Phenytoin