ArticleThe AAPS journal2016
A Whole-Body Physiologically Based Pharmacokinetic Model of Gefitinib in Mice and Scale-Up to Humans.
Article in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Utility of physiologically based pharmacokinetic (PBPK) modeling in oncology drug development and its accuracy: a systematic review.European journal of clinical pharmacology · 2018Pooled it
- Trial
- A structure-based modeling approach identifies effective drug combinations for RAS-mutant acute myeloid leukemia.iScience · 2026Article
- Dose-Response Relationship of Niclosamide and Metformin Combination in ApcGut and liver · 2026Article
- Maternal-Fetal Transfer and Toxicokinetics of 2,2',5,5'-Tetrachlorobiphenyl, [Chemical research in toxicology · 2025Article
- A whole-body mechanistic physiologically-based pharmacokinetic modeling of intravenous iron.Drug delivery and translational research · 2025Article
- Exploring the Impact of Pharmacological Target-Mediated Low Plasma Exposure in Lead Compound Selection in Drug Discovery - A Modeling Approach.The AAPS journal · 2024Article
- Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach.Antimicrobial agents and chemotherapy · 2024Article
- In Silico and In Vivo Pharmacokinetic Evaluation of 84-B10, a Novel Drug Candidate against Acute Kidney Injury and Chronic Kidney Disease.Molecules (Basel, Switzerland) · 2023Article
- In vitro and in vivo pharmacokinetic characterization, chiral conversion and PBPK scaling towards human PK simulation of S-MRI-1867, a drug candidate for Hermansky-Pudlak syndrome pulmonary fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity.CPT: pharmacometrics & systems pharmacology · 2023Article
- Vinblastine pharmacokinetics in mouse, dog, and human in the context of a physiologically based model incorporating tissue-specific drug binding, transport, and metabolism.Pharmacology research & perspectives · 2023Article
- Busting the Breast Cancer with AstraZeneca's Gefitinib.Advances in pharmacological and pharmaceutical sciences · 2023Review
- Prognostic value of sarcopenia in patients with lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors.Frontiers in nutrition · 2023Article
- Use of physiological based pharmacokinetic modeling for cross-species prediction of pharmacokinetic and tissue distribution profiles of a novel niclosamide prodrug.Frontiers in pharmacology · 2023Article
- Streamlining physiologically-based pharmacokinetic model design for intravenous delivery of nanoparticle drugs.CPT: pharmacometrics & systems pharmacology · 2022Article
- Migalastat Tissue Distribution: Extrapolation From Mice to Humans Using Pharmacokinetic Modeling and Comparison With Agalsidase Beta Tissue Distribution in Mice.Clinical pharmacology in drug development · 2021Article
- Article
- An HNSCC syngeneic mouse model for tumor immunology research and preclinical evaluation.International journal of molecular medicine · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gefitinib (Iressa) is a selective and potent EGFR tyrosine kinase inhibitor. It received an accelerated FDA approval in 2003 for the treatment of patients with nonsmall cell lung cancer (NSCLC) and represents the first-line therapy for NSCLC with EGFR mutations. In the work presented herein, the disposition of gefitinib was investigated extensively in mouse in both plasma and 11 organs (liver, heart, lung, spleen, gut, brain, skin, fat, eye, kidney, and muscle) after a single IV dose of 20 mg/kg. Gefitinib demonstrated extensive distribution in most tissues, except for the brain, and tissue to plasma partition coefficients (K pt) ranged from 0.71 (brain) to 40.5 (liver). A comprehensive whole-body physiologically based pharmacokinetic (PBPK) model of gefitinib in mice was developed, which adequately captured gefitinib concentration-time profiles in plasma and various tissues. Predicted plasma and tissue AUC values agreed well with the values calculated using the noncompartmental analysis (<25% difference). The PBPK model was further extrapolated to humans after taking into account the interspecies differences in physiological parameters. The simulated concentrations in human plasma were in line with the observed concentrations in healthy volunteers and patients with solid malignant tumors after both IV infusion and oral administration. Considering the extensive tissue distribution of gefitinib, plasma concentration may not be an ideal surrogate marker for gefitinib exposure at the target site or organ of toxicity (such as the skin). Since our whole-body PBPK model can predict gefitinib concentrations not only in plasma but also in various organs, our model may have clinical applications in efficacy and safety assessment of gefitinib.
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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.