ArticleCPT: pharmacometrics & systems pharmacology2019
Evaluation of the Drug-Drug Interaction Potential of Acalabrutinib and Its Active Metabolite, ACP-5862, Using a Physiologically-Based Pharmacokinetic Modeling Approach.
Article in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 46 citations in OpenAlex.
- Trial
- Acalabrutinib in Chronic Lymphocytic Leukemia: Pharmacology and Emerging Clinical Perspectives.European journal of haematology · 2026Review
- Pharmacokinetic Drug-Drug Interaction Potential of Oral Anticancer Drugs.Clinical pharmacology and therapeutics · 2026Article
- Physiologically Based Pharmacokinetic Modeling to Assess Antiretroviral-BTK Inhibitor Interactions and Provide Recommendations for Co-Administration Regimens.Pharmaceutics · 2026Article
- Inhibition of acalabrutinib metabolism by finerenone and its molecular docking studies.Cell biology and toxicology · 2026Article
- Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents.Cancers · 2024Review
- Evaluation of the potential impact on pharmacokinetics of various cytochrome P450 substrates of increasing IL-6 levels following administration of the T-cell bispecific engager glofitamab.CPT: pharmacometrics & systems pharmacology · 2024Article
- Utility of Physiologically Based Pharmacokinetic Modeling to Investigate the Impact of Physiological Changes of Pregnancy and Cancer on Oncology Drug Pharmacokinetics.Pharmaceutics · 2023Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- Recommendations on the use of azole antifungals in hematology-oncology patients.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2023Review
- Review
- Involvement of Transporters in Intestinal Drug-Drug Interactions of Oral Targeted Anticancer Drugs Assessed by Changes in Drug Absorption Time.Pharmaceutics · 2022Article
- Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors.Clinical pharmacology in drug development · 2022Article
- Alternatives to rifampicin: A review and perspectives on the choice of strong CYP3A inducers for clinical drug-drug interaction studies.Clinical and translational science · 2022Review
- Evaluation of the Pharmacokinetics and Safety of a Single Dose of Acalabrutinib in Subjects With Hepatic Impairment.Journal of clinical pharmacology · 2022Article
- Boosting the oral bioavailability of anticancer drugs through intentional drug-drug interactions.Basic & clinical pharmacology & toxicology · 2022Review
- Use of modeling and simulation to predict the influence of triazole antifungal agents on the pharmacokinetics of zanubrutinib and acalabrutinib.Frontiers in pharmacology · 2022Article
- Unraveling pleiotropic effects of rifampicin by using physiologically based pharmacokinetic modeling: Assessing the induction magnitude of P-glycoprotein-cytochrome P450 3A4 dual substrates.CPT: pharmacometrics & systems pharmacology · 2021Article
- Physiologically-Based Pharmacokinetic Modelling of Entrectinib Parent and Active Metabolite to Support Regulatory Decision-Making.European journal of drug metabolism and pharmacokinetics · 2021Article
- Vascular Impact of Cancer Therapies: The Case of BTK (Bruton Tyrosine Kinase) Inhibitors.Circulation research · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acalabrutinib, a selective, covalent Bruton tyrosine kinase inhibitor, is a CYP3A substrate and weak CYP3A/CYP2C8 inhibitor. A physiologically-based pharmacokinetic (PBPK) model was developed for acalabrutinib and its active metabolite ACP-5862 to predict potential drug-drug interactions (DDIs). The model indicated acalabrutinib would not perpetrate a CYP2C8 or CYP3A DDI with the sensitive CYP substrates rosiglitazone or midazolam, respectively. The model reasonably predicted clinically observed acalabrutinib DDI with the CYP3A perpetrators itraconazole (4.80-fold vs. 5.21-fold observed) and rifampicin (0.21-fold vs. 0.23-fold observed). An increase of two to threefold acalabrutinib area under the curve was predicted for coadministration with moderate CYP3A inhibitors. When both the parent drug and active metabolite (total active components) were considered, the magnitude of the CYP3A DDI was much less significant. PBPK dosing recommendations for DDIs should consider the magnitude of the parent drug excursion, relative to safe parent drug exposures, along with the excursion of total active components to best enable safe and adequate pharmacodynamic coverage.
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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.