JNCI Journal of the National Cancer Institute · 1988 · 13 citations · 0 references
MedicineOncologyPharmacologyCancer PharmacologyDose-response ModelingPharmacokinetic ModelingPharmacodynamics Of Anticancer AgentsPharmacodynamics Of Anticancer DrugsPharmacokinetics Of Anticancer DrugsConcentration - Time Profile AnalysisConcentration ProfilesConcentration-time Data AnalysisDose-time RelationshipDrug Toxicity ModelsPlasma Concentration - Time ProfilePlasma Concentration-time AnalysisPlasma Concentration-time Profile Analysis
We report a model that provides a strong correlation between mouse toxicity data [mouse lethal dose 10% (LD10)] and human plasma concentration-versus-time (CXT) data for 22 commonly used anticancer agents. Mouse toxicity data (LD10) from two dosing schedules, daily times one and daily times seven, were evaluated for the two mouse strains BDF/1 and Swiss. Data from BDF/1 mice were selected for analysis because they were more abundant. Strong correlations were found between LD10 and human plasma CXT data for both daily times one and daily times seven dosing schedules--ln (CXT) = -1.6504 + [0.8408 X ln (LD10)], r = .84, P less than .0001, and ln (CXT) = -0.0754 + [0.8954 X ln (LD10)], r = .90, P less than .0001, respectively. These correlations may serve as useful models to predict the maximally tolerated dose of an investigational anticancer agent prior to entry into clinical trials and to assist in the selection of clinically relevant in vitro CXTs for new-agent screening against human tumors.