Effects of ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of abemaciclib.
Eur J Clin Pharmacol
; 78(8): 1239-1247, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35527301
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzimidazóis
/
Neoplasias da Mama
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Subfamília B de Transportador de Cassetes de Ligação de ATP
/
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP
/
Aminopiridinas
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão