التفاصيل البيبلوغرافية
| العنوان: |
Effects of ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of abemaciclib. |
| المؤلفون: |
Maeda, Akimitsu, Ando, Hitoshi, Irie, Kei, Hashimoto, Naoya, Morishige, Jun-ichi, Fukushima, Shoji, Okada, Akira, Ebi, Hiromichi, Matsuzaki, Masahide, Iwata, Hiroji, Sawaki, Masataka |
| المصدر: |
European Journal of Clinical Pharmacology; Aug2022, Vol. 78 Issue 8, p1239-1247, 9p, 4 Charts, 1 Graph |
| مصطلحات موضوعية: |
DRUG tolerance, CONFIDENCE intervals, PROTEIN kinase inhibitors, GENETIC polymorphisms, ANTINEOPLASTIC agents, NEUTROPENIA, CANCER patients, DOSE-effect relationship in pharmacology, DESCRIPTIVE statistics, THROMBOCYTOPENIA, ODDS ratio, BREAST tumors |
| مستخلص: |
Purpose: Adverse events after the use of the CDK4/6 inhibitor abemaciclib are dose-dependent. However, its pharmacokinetics varies among individuals. Abemaciclib is reportedly transported by P-glycoprotein and breast cancer resistance protein. Therefore, we evaluated whether ABCB1 and ABCG2 polymorphisms are pharmacokinetic predictive factors of abemaciclib. Methods: A total of 45 patients with breast cancer taking abemaciclib (150 mg twice per day) for 2 weeks were evaluated to determine the associations among abemaciclib concentration; adverse events; and ABCB1 1236 T > C, 2677G > T/A, 3435C > T, and ABCG2 421C > A gene polymorphisms. Results: The trough concentration of abemaciclib was significantly higher in the group with grade 2 or greater neutropenia and thrombocytopenia than in those with grades 0 or 1. For ABCB1 2677G > T/A polymorphisms, the concentration of abemaciclib tended to be higher in the homozygous group (TT + AT) than in the wild-type + heterozygous group (GG + GA + GT) (median [range], 222.8 [80.5–295.8] ng/mL vs. 113.5 [23.6–355.2] ng/mL, P = 0.09), Moreover, the ABCB1 2677G > T/A homozygous group had a higher tendency of abemaciclib withdrawal or dose reduction within 4 weeks than the wild-type + heterozygous group (odds ratio, 4.22; 95% confidence interval, 0.86–20.7; P = 0.08). No significant association was observed among abemaciclib concentration; adverse reactions; and ABCB1 1236 T > C, 3435C > T, and ABCG2 421C > A polymorphisms. Conclusion: ABCB1 2677G > T/A polymorphism might be a predictor of the pharmacokinetics and tolerability of abemaciclib. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
