ArticleJournal of pharmacokinetics and pharmacodynamics2013
Physiologically based pharmacokinetic model of lapatinib developed in mice and scaled to humans.
Article in Journal of pharmacokinetics and pharmacodynamics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 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
- EGFR-ErbB2 dual kinase inhibitor lapatinib decreases autoantibody levels and worsens renal disease in Interferon α-accelerated murine lupus.International immunopharmacology · 2024Article
- Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.Acta pharmacologica Sinica · 2024Article
- Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice.Pharmaceutical research · 2023Article
- Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects.The Journal of clinical investigation · 2023Article
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- 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
- Proteomics of colorectal cancer liver metastasis: A quantitative focus on drug elimination and pharmacodynamics effects.British journal of clinical pharmacology · 2022Article
- Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood-Brain Barrier.Pharmaceutics · 2021Review
- Detoxication versus Bioactivation Pathways of Lapatinib In Vitro: UGT1A1 Catalyzes the Hepatic Glucuronidation of Debenzylated Lapatinib.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function.BMC cancer · 2021Article
- DREAM-in-CDM Approach and Identification of a New Generation of Anti-inflammatory Drugs Targeting mPGES-1.Scientific reports · 2020Article
- The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid.Investigational new drugs · 2020Article
- Predicting Paclitaxel Disposition in Humans With Whole-Body Physiologically-Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2019Article
- Pharmacokinetics of the Rac/Cdc42 Inhibitor MBQ-167 in Mice by Supercritical Fluid Chromatography-Tandem Mass Spectrometry.ACS omega · 2019Article
- Lapatinib-induced annexin A6 upregulation as an adaptive response of triple-negative breast cancer cells to EGFR tyrosine kinase inhibitors.Carcinogenesis · 2019Article
- Trimethoxystilbene Reduces Nuclear Factor Kappa B, Interleukin-6, and Tumor Necrosis Factor-BioMed research international · 2019Article
- A Multiscale Physiologically-Based Pharmacokinetic Model for Doxorubicin to Explore its Mechanisms of Cytotoxicity and Cardiotoxicity in Human Physiological Contexts.Pharmaceutical research · 2018Article
- Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making.Toxicological sciences : an official journal of the Society of Toxicology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Lapatinib is an oral 4-anilinoquinazoline derivative that dually inhibits epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This drug is a mere decade old and has only been approved by the FDA for the treatment of breast cancer since 2007. Consequently, the intricacies of the pharmacokinetics are still being elucidated. In the work presented herein, we determined the biodistribution of orally administered lapatinib in mouse plasma, brain, heart, lung, kidney, intestine, liver, muscle and adipose tissue. Using this data, we subsequently developed a physiologically based pharmacokinetic (PBPK) model of lapatinib in mice that accurately predicted the tissue concentrations after doses of 30, 60 and 90 mg/kg. By taking into account interspecies differences in physiology and physiochemistry, we then extrapolated the mouse PBPK model to humans. Our model predictions closely reflected lapatinib plasma pharmacokinetics in healthy subjects. Additionally, we were also able to simulate the pharmacokinetics of this drug in the plasma of patients with solid malignancies by incorporating a decrease in liver metabolism into the model. Finally, our PBPK model also facilitated the estimation of various human tissue exposures to lapatinib, which harmonize with the organ-specific toxicities observed in clinical trials. This first-generation PBPK model of lapatinib can be further improved with a greater understanding of lapatinib absorption, distribution, metabolism and excretion garnered from subsequent in vitro and in vivo studies and expanded to include other pharmacokinetic determinants, including efflux transporters, metabolite generation, combination dosing, etc., to better predict lapatinib disposition in both mouse and man.
Indexed as
Identifiers
What OpenQuestion holds
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.