Population Pharmacokinetics and Adverse Events of Erlotinib in Japanese Patients with Non-small-cell Lung Cancer: Impact of Genetic Polymorphisms in Metabolizing Enzymes and Transporters
| العنوان: | Population Pharmacokinetics and Adverse Events of Erlotinib in Japanese Patients with Non-small-cell Lung Cancer: Impact of Genetic Polymorphisms in Metabolizing Enzymes and Transporters |
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| المؤلفون: | Kosuke Kashiwabara, Akinobu Hamada, Yuki Kai, Chihiro Endo-Tsukude, Yukari Tsubata, Mitsuhiro Hayashi, Hideyuki Saito, Hirotsugu Kohrogi, Jiichiro Sasaki, Sho Saeki, Shinji Fujii, Sunao Ushijima, Hiroto Kishi, Megumi Inaba, Hiroshi Semba, Norihiro Iwamoto, Takeshi Isobe |
| المصدر: | Biological & Pharmaceutical Bulletin. 41:47-56 |
| بيانات النشر: | Pharmaceutical Society of Japan, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Oncology, medicine.medical_specialty, Lung Neoplasms, Drug-Related Side Effects and Adverse Reactions, Population, Pharmaceutical Science, Antineoplastic Agents, Single-nucleotide polymorphism, Models, Biological, Polymorphism, Single Nucleotide, 030226 pharmacology & pharmacy, Erlotinib Hydrochloride, 03 medical and health sciences, 0302 clinical medicine, Cytochrome P-450 Enzyme System, Carcinoma, Non-Small-Cell Lung, Internal medicine, Genotype, Humans, Medicine, Prospective Studies, Glucuronosyltransferase, Lung cancer, education, Adverse effect, Aged, Pharmacology, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Haplotype, General Medicine, medicine.disease, Rash, 030220 oncology & carcinogenesis, ATP-Binding Cassette Transporters, Female, Erlotinib, medicine.symptom, business, medicine.drug |
| الوصف: | Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model. The ABCB1 1236C>T (rs1128503) polymorphism, not ABCB1*2 haplotype (1236TT-2677TT-3455TT, rs1128503 TT-rs2032582 TT-rs1045642 TT), was a significant covariate for the apparent clearance (CL/F), with the TT genotype showing a 29.4% decrease in CL/F as compared with the CC and the CT genotypes. A marginally higher incidence of adverse events (mainly skin rash) was observed in the TT genotype group; however, patients with high plasma erlotinib exposure did not always experience skin rash. None of the other SNPs affected PK or adverse events. The ABCB1 genotype is a potential predictor for erlotinib adverse events. Erlotinib might be used with careful monitoring of adverse events in patients with ABCB1 polymorphic variants. |
| تدمد: | 1347-5215 0918-6158 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad494d53e885f53fe8ade834bbc85d6cTest https://doi.org/10.1248/bpb.b17-00521Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ad494d53e885f53fe8ade834bbc85d6c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13475215 09186158 |
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