| Autor: |
Yuta Nio, Hiroo Ishida, Natsumi Matsumoto, Sojiro Kusumoto, Yutaro Kubota, Takuya Tsunoda, Yasutsuna Sasaki, Ken-ichi Fujita |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
BMC Pulmonary Medicine, Vol 22, Iss 1, Pp 1-9 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2466 |
| DOI: |
10.1186/s12890-022-02249-8 |
| Popis: |
Abstract Background Gefitinib is recommended as a first-line treatment option for elderly patients with non-small cell lung cancer (NSCLC). Because no pharmacokinetics of gefitinib have been examined, we prospectively assessed the pharmacokinetics of gefitinib in patients with epidermal growth factor receptor gene-mutated advanced NSCLC who were 75 years or older. Methods Gefitinib was orally administered once daily at a dose of 250 mg. The concentrations of gefitinib and its major metabolite O-desmethyl gefitinib in plasma were measured by high-performance liquid chromatography. The area under the plasma concentration–time curve from time 0 to 48 h (AUC0–48) was calculated. Polymorphisms in CYP3A5, CYP2D6, ABCG2, ABCB1, and OATP1B1 were analyzed by direct sequencing. Results Eighteen patients with a median age of 80.5 years (range, 75–89) with adequate liver and kidney functions were examined. AUC0–48 values of gefitinib and O-desmethyl gefitinib in this population were 9.49 ± 3.5 and 10.6 ± 14 µM h, respectively. Compared to the gefitinib pharmacokinetics observed in a previous phase I study in Japan, systemic exposure to gefitinib in elderly patients was slightly higher than that in younger patients. Three patients experienced grade 3 diarrhea, increases in alanine aminotransferase, and aspartate aminotransferase levels 30 days after starting gefitinib treatment. The CYP2D6 genotype was associated with CYP2D6-mediated metabolism of gefitinib to O-desmethyl gefitinib. Conclusions We demonstrated for the first time the systemic exposure to gefitinib in elderly patients with NSCLC. Trial registration: The study was registered with the University Hospital Medical Information Network-Clinical Trials Registry Japan (UMIN000026409) on November 8, 2013. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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