ArticleActa pharmacologica Sinica2013
Pharmacokinetic-pharmacodynamic modeling of the anticancer effect of erlotinib in a human non-small cell lung cancer xenograft mouse model.
Article in Acta pharmacologica Sinica, 2013. 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, 20 citations in OpenAlex.
- Phase I/II Study of Erlotinib to Determine the Optimal Dose in Patients With Non-Small Cell Lung Cancer Harboring Only EGFR Mutations.Clinical and translational science · 2020Trial
- Protective Effects of Adenosine Triphosphate and Flunarizine on Erlotinib-Induced Ovarian Damage: An Experimental Study.Life (Basel, Switzerland) · 2026Article
- Article
- An Orally Available Grafted Peptide Targeting Epidermal Growth Factor Receptor Dimers Reduces Non-Small Cell Lung Cancer Tumors in Mouse Models.ACS pharmacology & translational science · 2025Article
- GRHL2-HER3 and E-cadherin mediate EGFR-bypass drug resistance in lung cancer cells.Frontiers in cell and developmental biology · 2024Article
- Article
- A flexible electronic strain sensor for the real-time monitoring of tumor regression.Science advances · 2022Article
- Weekly osimertinib dosing prevents EGFR mutant tumor cells destined to home mouse lungs.Translational oncology · 2021Article
- Mathematical Approach to Differentiate Spontaneous and Induced Evolution to Drug Resistance During Cancer Treatment.JCO clinical cancer informatics · 2019Article
- Antitumor effect of axitinib combined with dopamine and PK-PD modeling in the treatment of human breast cancer xenograft.Acta pharmacologica Sinica · 2019Article
- Survival Prolongation Index as a Novel Metric to Assess Anti-Tumor Activity in Xenograft Models.The AAPS journal · 2019Article
- Assessment of non-linear combination effect terms for drug-drug interactions.Journal of pharmacokinetics and pharmacodynamics · 2016Review
- Pharmacokinetic-pharmacodynamic modeling of the antitumor effect of TM208 and EGFR-TKI resistance in human breast cancer xenograft mice.Acta pharmacologica Sinica · 2016Article
- Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2016Article
- Analysis of the lipidome of xenografts using MALDI-IMS and UHPLC-ESI-QTOF.Journal of the American Society for Mass Spectrometry · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimErlotinib is used to treat non-small-cell lung cancer (NSCLC), which targets epidermal growth factor receptor (EGFR) tyrosine kinase. The aim of this study was to investigate the relationship between erlotinib plasma concentrations and phosphorylated EGFR (pEGFR) levels, as well as the relationship between pEGFR levels and tumor growth inhibition in a human non-small-cell lung cancer xenograft mouse model.
methodsFemale BALB/c nude mice were implanted with the human NSCLC cell line SPC-A-1. The animals were given via gavage a single dose of erlotinib (4, 12.5, or 50 mg/kg). Pharmacokinetics of erlotinib was determined using LC-MS/MS. Tumor volume and pEGFR levels in tumor tissues were measured at different time points after erlotinib administration. The levels of pEGFR in tumor tissues was detected using Western blotting and ELISA assays.
resultsThe pharmacokinetics of erlotinib was described by a two-compartment model with first order extravascular absorption kinetics. There was a time delay of approximately 2 h between erlotinib plasma concentrations and pEGFR degradation. The time course of pEGFR degradation was reasonably fit by the indirect response model with a calculated IC50 value of 1.80 μg/mL. The relationship between pEGFR levels and tumor volume was characterized by the integrated model with a Kbio value of 0.507 cm(3)/week, which described the impact of pEGFR degradation on tumor growth.
conclusionThe pharmacokinetic/pharmacodynamic properties of erlotinib in a human tumor xenograft model were described by the indirect response model and integrated model, which will be helpful in understanding the detailed processes of erlotinib activity and determining an appropriate dosing regimen in clinical studies.
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