ReviewClinical pharmacokinetics2020
Clinical Pharmacokinetics and Pharmacodynamics of the Cyclin-Dependent Kinase 4 and 6 Inhibitors Palbociclib, Ribociclib, and Abemaciclib.
Review in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Adjuvant and neoadjuvant therapy with or without CDK4/6 inhibitors in HR+/HER2- early breast cancer: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Systematic review of the management of brain metastases from hormone receptor positive breast cancer.Journal of neuro-oncology · 2023Pooled it
- Models of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.International journal of molecular sciences · 2025Trial
- Can thromboprophylaxis build a link for cancer patients undergoing surgical and/or chemotherapy treatment? The MeTHOS cohort study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Trial
- Bioequivalence Study of Palbociclib Capsules in Healthy Chinese Subjects Under Fasting and Fed Conditions.Clinical drug investigation · 2022Trial
- Genetic Variation inInternational journal of molecular sciences · 2026Article
- CDK4/6 Inhibitors in Breast Cancer Therapy: Mechanisms, Resistance, and Emerging Opportunities.Targeted oncology · 2026Review
- Review
- Divergent neuropsychiatric and systemic toxicity profiles of abemaciclib and palbociclib: a triangulation study integrating pharmacovigilance, genetic epidemiology, and multi-omics profiling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Global Trends in Integrating Machine Learning (ML) with Model-Informed Drug Development (MIDD): A Bibliometric and Systematic Review (2015-2025).Pharmaceutics · 2026Review
- Austrian treatment algorithms 2025: CDK 4/6 inhibitors in the adjuvant therapy of HR+/HER2- early breast cancer.Wiener klinische Wochenschrift · 2026Review
- Next Frontier in HER2+/HR+ Breast Cancer: Leveraging Cell Cycle Control with CDK4/6 Inhibitors.Journal of personalized medicine · 2026Review
- Prospective monitoring of plasma abemaciclib in breast cancer patients: associations with age and adverse events.Cancer chemotherapy and pharmacology · 2026Article
- The Absorption, Distribution, Excretion, and In Vitro Hepatic Microsomal Metabolism of the Novel CDK Compound XMD12 in Sprague-Dawley Rats.Pharmaceutics · 2025Article
- Targeting menin in lysine methyltransferase 2A/nucleophosmin-mutated leukemia: A novel strategy from epigenetic dysregulation to clinical therapy (Review).Oncology letters · 2025Review
- Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.Oncogene · 2025Article
- Article
- Dinaciclib Interrupts Cell Cycle and Induces Apoptosis in Oral Squamous Cell Carcinoma: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Article
- Review
- Binding Mechanism of Inhibitors to CDK6 Deciphered by Multiple Independent Molecular Dynamics Simulations and Free Energy Predictions.Molecules (Basel, Switzerland) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palbociclib, ribociclib, and abemaciclib are inhibitors of the cyclin-dependent kinases 4 and 6 approved for the treatment of locally advanced or metastatic breast cancer. In this review, we provide an overview of the available clinical pharmacokinetic and pharmacodynamic characteristics of these novel drugs, summarize the results of food-effect and drug-drug interaction studies, and highlight exposure-response and exposure-toxicity relationships. All three drugs exhibit a large inter-individual variability in exposure (coefficient of variation range 40-95% for minimum plasma concentration), are extensively metabolized by cytochrome P450 3A4, and have their brain penetration limited by efflux transporters. Abemaciclib has three active metabolites with similar potency that are clinically relevant (i.e., M2, M20, M18), whereas the metabolites of palbociclib and ribociclib are not of clinical significance. Pharmacokinetic exposure increases in a dose-proportional manner for palbociclib, whereas exposure increases under- and over-proportionally with an increasing dose for abemaciclib and ribociclib, respectively. High exposure is associated with an increased risk of neutropenia, and for ribociclib also to corrected QT prolongation. For abemaciclib, a clear exposure-efficacy relationship has been described, while for palbociclib and ribociclib exposure-response analyses remain inconclusive. Future studies are needed to address exposure-efficacy relationships to further improve dosing.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.