Effects of ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of abemaciclib

Maeda, Akimitsu; Ando, Hitoshi; Irie, Kei; Ebi, Hiromichi

doi:10.1007/s00228-022-03331-0

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…Other reports supported the relationship between ABCB1 homozygous polymorphisms (2677G>T/A) and increased ABE toxicity, due to higher concentrations of its active metabolites M2 and M20. 60 , 61 …”

Section: Abe Pharmacological Interactionsmentioning

confidence: 99%

Abemaciclib pharmacology and interactions in the treatment of HR+/HER2− breast cancer: a critical review

Martorana,

Sanò,

Valerio

et al. 2024

Therapeutic Advances in Drug Safety

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Abemaciclib (ABE) in combination with endocrine therapy represents the mainstay treatment for either endocrine-resistant metastatic or high-risk early-stage HR+/HER2− breast cancer patients. Hence, an adequate knowledge of this agent pharmacodynamic, pharmacokinetic, and of its drug–drug interactions (DDIs) is crucial for an optimal patients management. Additionally, ABE interference with food and complementary/alternative medicines should be taken into account in the clinical practice. Several online tools allow to freely check DDIs and can be easily consulted before prescribing ABE. According to one of this instruments, ABE display the lowest number of interactions among the available cyclin-dependent kinase 4/6 inhibitors. Still, clinicians should be aware that online tools cannot replace the technical datasheet of the drug as well as a comprehensive clinical assessment for each patient. Here we critically review the main pharmacological features of ABE, then focusing on its potential interactions with drugs, food, and alternative medicine, in order to provide a guide for its optimal use in the treatment of HR+/HER2− breast cancer patients.

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Section: Abe Pharmacological Interactionsmentioning

confidence: 99%

Abemaciclib pharmacology and interactions in the treatment of HR+/HER2− breast cancer: a critical review

Martorana,

Sanò,

Valerio

et al. 2024

Therapeutic Advances in Drug Safety

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“…Studies have investigated the relationship between CDK4/6i and efflux transporters. Abemaciclib concentrations are higher when ABCB1 2677G>T/A is homozygous ( Maeda et al, 2022 ; Maeda et al, 2023 ). Palbociclib oral absorption and plasma levels may be affected by ABCB1-rs1128503, rs1045642, and rs2032582 ( Roncato et al, 2022 ).…”

Section: Metabolic and Transport Differencesmentioning

confidence: 99%

“…-Responsible for metabolizing 26% of Palbociclib (Yu et al, 2017) -ABCB1 ABCB1 2677G>T/A homozygous type is associated with a higher abemaciclib concentration (Maeda et al, 2022;Maeda et al, 2023) Palbociclib resistance is mediated by ABCB1 (Fu et al, 2022) Substrate and potent inhibitor of ABCB1 (Sorf et al, 2018) Remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer (Wu et al, 2017) ABCB1_rs1128503 is potential risk factors for neutropenia (Iwata et al, 2021) P-glycoprotein limits Ribociclib brain exposure (Martínez-Chávez et al, 2019) ABCB1 limit brain penetration and total plasma exposure of abemaciclib (Martínez-Chávez et al, 2022) Palbociclib is a substrate of P-gp (de Gooijer et al, 2015) ABCB1-rs1128503, rs1045642, and rs2032582 may increase oral drug absorption and plasma concentration (Roncato et al, 2022) ABCG2 ABCG2 limit brain penetration and total plasma exposure of abemaciclib (Martínez-Chávez et al, 2022) Palbociclib is a substrate of BCRP (de Gooijer et al, 2015) Ribociclib as a potent inhibitor of ABCG2 (Sorf et al, 2018) OATP1B1 -Fatal Statin induced rhabdomyolysis by possible interaction with Palbociclib through OATP1B1 (Nelson et al, 2017) Ribociclib can potentially inhibit OATP1B1 (Streicher et al, 2021) OATP1B3 --Ribociclib can potentially inhibit OATP1B3 (Streicher et al, 2021) Frontiers in Pharmacology frontiersin.org the metabolic and transport variations and resistance differences of the three CDK4/6i (Abemaciclib, Palbociclib, and Ribociclib) that have been approved by the FDA for treating tumors. It also aims to discuss how these differences impact the effectiveness and safety of anticancer drugs.…”

Section: Sult2a1mentioning

confidence: 99%

Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib

Zhu

2023

Front. Pharmacol.

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Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) play a crucial role in cancer treatment, particularly in breast cancer, and their mechanism of drug resistance is a topic of global interest in research. Hence, it is vital to comprehend the distinctions between various CDK4/6i, including their mechanisms of action and resistance mechanisms. This article aims to summarize the metabolic and transport variations as well as the differences in resistance among the three FDA-approved CDK4/6 inhibitors: Abemaciclib, Palbociclib, and Ribociclib. It also aims to discuss how these differences impact the effectiveness and safety of anticancer drugs. It was conducted in March 2023 to search PubMed, Embase, and Web of Science for literature related to this topic. Despite all being CDK4/6i, differences in their metabolism and transport were found, which are related to their chemical structure. Moreover, there are variations in preclinical pharmacology, pharmacokinetics, and clinical safety and efficacy of the different inhibitors. Genetic mutations, drug tolerance, and other factors may influence CDK4/6 resistance mechanisms. Currently, the resistance mechanisms differences of the three drugs remain largely unknown, and there are differences in the resistance mechanisms among them, necessitating further exploration and research.

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“…Several studies have linked this variant to a different response of pharmacological treatments for diseases such as epilepsy, HIV, coagulation disorders and different types of cancer [ 17 , 18 , 19 , 20 ]. Moreover, an exhaustive investigation about rs2032582 genotypes and haplotypes of the ABCB1 gene was reported [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

An Improved Technique for Genotyping the ABCB1 Gene Variant of Exon 21

Zuccoli

Pagnotta

Melito

et al. 2023

MPs

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The Multidrug Resistance protein (ABCB1, MDR1) is involved in the transport of xenobiotics and antiretroviral drugs. Some variants of the ABCB1 gene are of clinical importance; among them, exon 12 (c.1236C>T, rs1128503), 21 (c.2677G>T/A, rs2032582), and 26 (c.3435C>T, rs1045642) have a high incidence in Caucasians. Several protocols have been used for genotyping the exon 21 variants, such as allele-specific PCR-RFLP using adapted primer to generate a digestion site for several enzymes and automatic sequencing to detect the SNVs, TaqMan Allele Discrimination assay and High-Resolution Melter analysis (HRMA). The aim was to describe a new approach to genotype the three variants c.2677G>T/A for the exon 21 doing only one PCR with the corresponding primers and the digestion of the PCR product with two restriction enzymes: BrsI to identify A allele and BseYI to differentiate between G or T. An improvement of this methodology was also described. The proposal technique here described is demonstrated to be very efficient, easy, fast, reproducible, and cost-effective.

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Effects of ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of abemaciclib

Cited by 6 publications

References 33 publications

Abemaciclib pharmacology and interactions in the treatment of HR+/HER2− breast cancer: a critical review

Abemaciclib pharmacology and interactions in the treatment of HR+/HER2− breast cancer: a critical review

Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib

An Improved Technique for Genotyping the ABCB1 Gene Variant of Exon 21

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