Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB 1 polymorphism
| العنوان: | Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with |
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| المؤلفون: | Shintaro Kanda, Yasushi Goto, Yutaka Fujiwara, Hiroaki Aikawa, Yuichiro Ohe, Akinobu Hamada, Toshiyuki Hata, Noboru Yamamoto, Hidehito Horinouchi, Hiroshi Nokihara, Kota Itahashi, Hidenori Mizugaki |
| المصدر: | Cancer Science |
| بيانات النشر: | Wiley, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, Cancer Research, Lung Neoplasms, Pyridines, Pharmacology, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, Japan, Carcinoma, Non-Small-Cell Lung, Anaplastic Lymphoma Kinase, non‐small‐cell lung cancer, Standard treatment, Interstitial lung disease, General Medicine, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Toxicity, Original Article, Female, Median body, pharmacokinetics, medicine.drug, medicine.medical_specialty, ATP Binding Cassette Transporter, Subfamily B, Genotype, Polymorphism, Single Nucleotide, 03 medical and health sciences, Crizotinib, Asian People, Pharmacokinetics, Clinical Research, Internal medicine, medicine, Humans, Adverse effect, Lung cancer, Aged, pharmacogenomics, Polymorphism, Genetic, business.industry, Body Weight, Receptor Protein-Tyrosine Kinases, Original Articles, medicine.disease, EML4–ALK fusion protein, Pyrazoles, business |
| الوصف: | Crizotinib is a standard treatment for advanced ALK‐positive non‐small‐cell lung cancer (NSCLC). We undertook this study to investigate the pharmacokinetics of crizotinib and clinical and pharmacogenomic factors that may increase the risk of adverse events (AEs). We defined clinically significant AEs as grade 4 hematological toxicity, grade ≥3 non‐hematological toxicity, and any grade of interstitial lung disease. Eight subjects with ALK‐positive NSCLC scheduled to receive crizotinib 250 mg twice daily were studied. Six patients were female and two were male, and most of the patients had low body weight with a median body weight of 46.8 kg (range, 42.4–61.0 kg). All patients developed AEs, five developing six clinically significant AEs. Six patients required dose reduction. In pharmacokinetic analysis, blood samples were obtained on days 1 and 15. The mean area under the plasma concentration–time curve from 0–12 h (AUC 0–12) on day 15 was significantly increased in patients with clinically significant AEs (n = 5) compared with those without (n = 3) (P = 0.04). Genetic polymorphisms of ABCB1 were analyzed. One patient with the ABCB1 1236TT‐2677TT‐3435TT genotype was an outlier, with an AUC 0–12 and peak concentrations on day 15 of 2.84× and 2.61× the mean, respectively, compared with those with other genotypes. Our results suggest that some Japanese NSCLC patients treated with crizotinib developed clinically significant toxicities that were related to altered pharmacokinetics parameters due to genotype and body weight factors. |
| تدمد: | 1349-7006 1347-9032 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::371be2bb081e5e83c9bad3489768ea61Test https://doi.org/10.1111/cas.12983Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....371be2bb081e5e83c9bad3489768ea61 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 13479032 |
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