Associations among plasma concentrations of regorafenib and its metabolites, adverse events, and ABCG2 polymorphisms in patients with metastatic colorectal cancers
| Autor: | Koki Hashimoto, Erika Sugiyama, Mitsukuni Suenaga, Kazuyoshi Kawakami, Hiyori Kidokoro, Takeru Wakatsuki, Masataka Tajima, Keisho Chin, Eiji Shinozaki, Hitoshi Sato, Takashi Ichimura, Yuichi Minowa, Wataru Suzuki, Yasuhiro Nakano, Izuma Nakayama, Kazuo Kobayashi, Mariko Ogura, Toshihiro Hama, Daisuke Takahari, Akira Ooki, Tomoko Hiraoka, Kensei Yamaguchi, Takashi Yokokawa, Takeshi Aoyama, Kenichi Suzuki |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty medicine.drug_class Colorectal cancer Bilirubin Toxicology Gastroenterology Tyrosine-kinase inhibitor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Internal medicine Regorafenib medicine Pharmacology (medical) Adverse effect Pharmacology biology business.industry medicine.disease Rash 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis biology.protein medicine.symptom SLCO1B1 business |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 87:767-777 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | The association between the pharmacokinetics and pharmacodynamics of regorafenib, a multiple tyrosine kinase inhibitor, remains unclear. This study assessed the trough plasma concentrations (Ctrough) of regorafenib and its N-oxide (M2) and N-oxide/desmethyl (M5) metabolites, and evaluated the associations among these levels, adverse events, and pharmacokinetic-related genetic polymorphisms in patients with metastatic colorectal cancer. The Ctrough levels of regorafenib and its metabolites were assessed in a single-center, prospective, observational study, 7 days after the initial treatment. The correlation between those values and adverse events was then examined. In addition, the genetic polymorphisms of ABCG2, SLCO1B1, and UGT1A9 were determined and evaluated for associations with the levels of regorafenib, M2, and M5. We analyzed 43 patients who received regorafenib 40–120 mg/day; among them, 35 patients started at 120 mg/day. With regard to bilirubin increase, the Ctrough values of regorafenib were significantly higher in the group with grade ≥ 2 than in groups with grades 0 and 1 (p = 0.010). The M5 Ctrough levels were significantly associated with the severity of hypertension or rash (p |
| Databáze: | OpenAIRE |
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