ArticleThe AAPS journal2012
A physiologically based pharmacokinetic model of mitoxantrone in mice and scale-up to humans: a semi-mechanistic model incorporating DNA and protein binding.
Article in The AAPS journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
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- Nanomedicines in diagnosis and treatment of prostate cancers: an updated review.Frontiers in bioengineering and biotechnology · 2024Review
- No Interference of H9 Extract on Trastuzumab Pharmacokinetics in Their Combinations.International journal of molecular sciences · 2023Article
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- Evaluation of Pharmacokinetic Feasibility of Febuxostat/L-pyroglutamic Acid Cocrystals in Rats and Mice.Pharmaceutics · 2023Article
- Multiscale and Translational Quantitative Systems Toxicology, Pharmacokinetic-Toxicodynamic Modeling Analysis for Assessment of Doxorubicin-Induced Cardiotoxicity.The AAPS journal · 2021Article
- Dynamical Boolean Modeling of Immunogenic Cell Death.Frontiers in physiology · 2020Article
- Pilot study comparing serum chemotherapy levels after intra-arterial and intravenous administration in dogs with naturally occurring urinary tract tumors.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2019Article
- A Multiscale Physiologically-Based Pharmacokinetic Model for Doxorubicin to Explore its Mechanisms of Cytotoxicity and Cardiotoxicity in Human Physiological Contexts.Pharmaceutical research · 2018Article
- Characterization and Interspecies Scaling of rhTNF-Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Inherited variation in OATP1B1 is associated with treatment outcome in acute myeloid leukemia.Clinical pharmacology and therapeutics · 2016Article
- A Whole-Body Physiologically Based Pharmacokinetic Model of Gefitinib in Mice and Scale-Up to Humans.The AAPS journal · 2016Article
- Article
- Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.The AAPS journal · 2013Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We conducted a pharmacokinetic (PK) study of mitoxantrone (Novantrone®), a clinically well-established anticancer agent, in mice and developed a mechanism-based PBPK (physiologically based pharmacokinetic) model to describe its disposition. Mitoxantrone concentrations in plasma and six organs (lung, heart, liver, kidney, spleen, and brain) were determined after a 5 mg/kg i.v. dose. We evaluated three different PBPK models in order to characterize our experimental data: model 1 containing Kp values, model 2 incorporating a deep binding compartment, and model 3 incorporating binding of mitoxantrone to DNA and protein. Among the three models, only model 3 with DNA and protein binding captured all the experimental data well. The estimated binding affinity for DNA (K (DNA)) and protein (K (macro)) were 0.0013 and 1.44 μM, respectively. Predicted plasma and tissue AUC values differed from observed values by <19 %, except for heart (60 %). Model 3 was further used to simulate plasma mitoxantrone concentrations in humans for a 12-mg/m(2) dose, using human physiological parameters. The simulated results generally agreed with the observed time course of mitoxantrone plasma concentrations in patients after a standard dose of 12 mg/m(2). In summary, we reported for the first time a mechanism-based PBPK model of mitoxantrone incorporating macromolecule binding which may have clinical applicability in optimizing clinical therapy. Since mitoxantrone is a substrate of the efflux transporters ABCG2 and ABCB1, the incorporation of efflux transporters may also be necessary to characterize the data obtained in low-dose studies.
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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.