生理藥代動力學模型在EGFR-TKI精準治療中的應用進展

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中圖分類號R969.1；R969.3 文獻標志碼A 文章編號1001-0408（2025）08-1013-06

DOI 10.6039/j.issn.1001-0408.2025.08.22

Advances in the application of physiologically-based pharmacokinetic model in EGFR-TKI precision therapy

YANG Yingying'，SHAO Jiaqi'2，XIANG Qiulin'，LI Guoxing'，YU Xian'（1. Phase I Clinical Trial Center， the Second Ailiated Hospital of Chongqing Medical University， Chongqing 400o60，China； 2.College of Pharmacy，Chongqing Medical University， Chongqing 400016，China）

ABSTRACTEpidermalgrowthfactorreceptor-tyrosinekinase inhibitor（EGFR-TKI）representaclassof small-molecule targeted therapeuticsforoncologytreatmentandserveafrst-linetherapyforadvancednonsmallcellungcancer（NSCLC）withEGFRsensitivemutations，withrepresentativeagentsincludinggefitinib，dacomitinib，andosimertinibInclinicalpractice，dose adjustmentofEGFR-TKImay be required forcancer patients under specialcircumstances suchas drug combinationsorhepatic/ renalmpairment.Physiologically-basedphamacokinetic（PBPK）model，capableofpredicting pharmacokinetic（PK）procesesin humans，hasemergedasavitaltolforclinicaldoseptimizationThiarticlesortsthemodelingmethodologiesworkflowsand commonly usedsoftwaretoosforPBPKmodelandsummarizesthecurrent applicationsofPBPKmodelinEGFR-KIprecision therapyasofJune 30，2024.Findings demonstratethat PBPK modeling methodscommonlyemploythe“botom-up"approach and themidle-outapproach.The processtypicallinvolvesfoursteps：parametercolectin，ompartment selection，modelalidatio， andmodeaplication.Commonlyusedsoftwarefor modeling includes Simcyp，GastroPlus，andopen-sourcesoftwaresuchasPKSim.PBPKmodelcanbeutilizedfor predictingdrug-drug interactionsof EGFR-TKIco-administered withmetabolic enzyme inducersorinhibitors，acid-suppressivedrugs，ortraditionalChineseandWestermmedicines.Itcanalsoadjustdosagesin conjunctionwithgenomics，predictPKprocesses inspecialpopulations（suchas patientswithliverorkidneydysfunctionpediatric patients），evaluatethe efficacyand safety of drugs，and extrapolate PK predictions fromanimal models to humans.

KEYWODSphysiologicall-based pharmacokinetic model；EGFR-TKI；precision treatment；drug interaction；non-smallcell lung cancer

表皮生長因子受體（epidermal growth factor receptor，EGFR）基因突變是非小細胞肺癌（non-smallcell lungcancer，NSCLC）常見的致癌驅(qū)動突變，EGFR突變會顯著增強腫瘤細胞的生長和分裂能力，加速腫瘤發(fā)展。（剩余13989字）