ArticleCancer chemotherapy and pharmacology2017
A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model of the histone deacetylase (HDAC) inhibitor vorinostat for pediatric and adult patients and its application for dose specification.
Article in Cancer chemotherapy and pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review.Clinical pharmacokinetics · 2026Review
- Practical Pharmacokinetic-Pharmacodynamic Models in Oncology.Pharmaceutics · 2025Review
- Comparison of Relative Activity versus Relative Expression Factors (RAF versus REF) in Predicting Glucuronidation Mediated Drug Clearance Using Recombinant UGTs.Pharmaceutical research · 2024Article
- Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy.Cancer research · 2024Article
- Gesicles packaging dCas9-VPR ribonucleoprotein complexes can combine with vorinostat and promote HIV proviral transcription.Molecular therapy. Methods & clinical development · 2024Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- Predicting the correct dose in children: Role of computational Pediatric Physiological-based pharmacokinetics modeling tools.CPT: pharmacometrics & systems pharmacology · 2023Review
- Leveraging modeling and simulation to optimize the therapeutic window for epigenetic modifier drugs.Pharmacology & therapeutics · 2022Review
- Targeting the epigenome in in-stent restenosis: from mechanisms to therapy.Molecular therapy. Nucleic acids · 2021Review
- A Physiologically Based Pharmacokinetic-Pharmacodynamic Model for Capecitabine in Colorectal Cancer Rats: Simulation of Antitumor Efficacy at Various Administration Schedules.European journal of drug metabolism and pharmacokinetics · 2021Article
- Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- High-throughput screening identifies histone deacetylase inhibitors that modulate GTF2I expression in 7q11.23 microduplication autism spectrum disorder patient-derived cortical neurons.Molecular autism · 2020Article
- Physiologically-Based Pharmacokinetic (PBPK) Modeling Providing Insights into Fentanyl Pharmacokinetics in Adults and Pediatric Patients.Pharmaceutics · 2020Article
- Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review.Journal of clinical medicine · 2020Review
- Toward precision medicine in pediatric population using cytochrome P450 phenotyping approaches and physiologically based pharmacokinetic modeling.Pediatric research · 2020Review
- Computational Approaches in Preclinical Studies on Drug Discovery and Development.Frontiers in chemistry · 2020Review
- Guiding dose adjustment of amlodipine after co-administration with ritonavir containing regimens using a physiologically-based pharmacokinetic/pharmacodynamic model.Journal of pharmacokinetics and pharmacodynamics · 2018Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
purposeThis study aimed at recommending pediatric dosages of the histone deacetylase (HDAC) inhibitor vorinostat and potentially more effective adult dosing regimens than the approved standard dosing regimen of 400 mg/day, using a comprehensive physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling approach.
methodsA PBPK/PD model for vorinostat was developed for predictions in adults and children. It includes the maturation of relevant metabolizing enzymes. The PBPK model was expanded by (1) effect compartments to describe vorinostat concentration-time profiles in peripheral blood mononuclear cells (PBMCs), (2) an indirect response model to predict the HDAC inhibition, and (3) a thrombocyte model to predict the dose-limiting thrombocytopenia. Parameterization of drug and system-specific processes was based on published and unpublished in silico, in vivo, and in vitro data. The PBPK modeling software used was PK-Sim and MoBi.
resultsThe PBPK/PD model suggests dosages of 80 and 230 mg/m
conclusionsThoroughly developed PBPK models enable dosage recommendations in pediatric patients and integrated PBPK/PD models, considering PD biomarkers (e.g., HDAC activity and platelet count), are well suited to guide future efficacy trials by identifying dosing regimens potentially superior to standard dosing regimens.
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