Trial reportClinical pharmacokinetics2019
Population Pharmacokinetics of the BTK Inhibitor Acalabrutinib and its Active Metabolite in Healthy Volunteers and Patients with B-Cell Malignancies.
Trial report in Clinical pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Assessment of ethnic differences in pharmacokinetics and clinical responses of acalabrutinib between Chinese and White patients with B-cell malignancies.British journal of clinical pharmacology · 2025Trial
- Quantitative Systems Pharmacology Model to Predict Target Occupancy by Bruton Tyrosine Kinase Inhibitors in Patients With B-Cell Malignancies.CPT: pharmacometrics & systems pharmacology · 2025Article
- Solid lipid nanoparticles for increased oral bioavailability of acalabrutinib in chronic lymphocytic leukaemia.Discover nano · 2024Article
- Review
- Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors.Clinical pharmacology in drug development · 2022Article
- Effect of autoinduction and food on the pharmacokinetics of furmonertinib and its active metabolite characterized by a population pharmacokinetic model.Acta pharmacologica Sinica · 2022Article
- Evaluation of the Pharmacokinetics and Safety of a Single Dose of Acalabrutinib in Subjects With Hepatic Impairment.Journal of clinical pharmacology · 2022Article
- Improved characterization of the pharmacokinetics of acalabrutinib and its pharmacologically active metabolite, ACP-5862, in patients with B-cell malignancies and in healthy subjects using a population pharmacokinetic approach.British journal of clinical pharmacology · 2022Article
- Evaluation of the Drug-Drug Interaction Potential of Acalabrutinib and Its Active Metabolite, ACP-5862, Using a Physiologically-Based Pharmacokinetic Modeling Approach.CPT: pharmacometrics & systems pharmacology · 2019Article
- Pharmacokinetic-pharmacodynamic models that incorporate drug-target binding kinetics.Current opinion in chemical biology · 2019Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionBruton tyrosine kinase (BTK) is a key component of B-cell receptor signalling, critical for cell proliferation. Acalabrutinib, a selective, covalent BTK inhibitor, recently received an accelerated approval in relapsed/refractory mantle cell lymphoma. This analysis characterized the population pharmacokinetics (PK) of acalabrutinib and its metabolite ACP-5862.
methodsData were obtained from six phase I/II trials in adult patients with B-cell malignancy and seven phase I trials in healthy volunteers. Pooled concentration-time data, at dose levels ranging from 15 to 400 mg, were analysed using non-linear mixed-effects modelling. Base model parameters were scaled with body weight and normalized to 70 kg (fixed exponents: 0.75 and 1 for clearance and volumes, respectively). A full covariate approach was used to evaluate any relevant effects of dose, health group/disease status, hepatic and renal impairment, use of acid-reducing agents, race and sex.
resultsA total of 11,196 acalabrutinib and 1068 ACP-5862 concentration-time samples were available. The PK of both analytes were well described using two-compartment disposition models. Acalabrutinib absorption was characterized using sequential zero- and first-order constants and a lag time. Apparent clearance (CL/F) of acalabrutinib was 169 L/h (95% CI 159-175). Relative to the 100 mg dose group, the 15 and 400 mg dose groups showed a 1.44-fold higher and 0.77-fold lower CL/F, respectively. The clearance for ACP-5862 was 21.9 L/h (95% CI 19.5-24.0). The fraction metabolized was fixed to 0.4. The central and peripheral volumes of distribution were 33.1 L (95% CI 24.4-41.0) and 226 L (95% CI 149-305) for acalabrutinib, and 38.5 L (95% CI 31.6-49.2) and 38.4 L (95% CI 32.3-47.9) for ACP-5862. None of the investigated covariates led to clinically meaningful changes in exposure.
conclusionThe PK of acalabrutinib and its metabolite ACP-5862 were adequately characterized. Acalabrutinib CL/F decreased with increasing dose, but the trend was small over the 75-250 mg range. No dose adjustment was necessary for intrinsic or extrinsic covariates.
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