2020
Physiologically Based Pharmacokinetic Modeling in Risk Assessment: Case Study With Pyrethroids
Mallick P, Song G, Efremenko A, Pendse S, Creek M, Osimitz T, Hines R, Hinderliter P, Clewell H, Lake B, Yoon M, Moreau M. Physiologically Based Pharmacokinetic Modeling in Risk Assessment: Case Study With Pyrethroids. Toxicological Sciences 2020, 176: 460-469. PMID: 32421774, PMCID: PMC7416317, DOI: 10.1093/toxsci/kfaa070.Peer-Reviewed Original ResearchConceptsAge-related pharmacokinetic differencesPharmacokinetic differencesPBPK modelTarget tissue exposureAge-related sensitivityHuman PBPK modelAge-dependent changesAge-related differencesRat modelTissue exposureVivo rat dataPharmacokinetic modellingPharmacokinetic modelingInternal exposureRat dataRisk assessmentVivo extrapolationRisk assessment purposesExposureAdultsExternal exposureSensitive populationsChildrenMetabolic capacityAssessment
2019
Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans
Mallick P, Moreau M, Song G, Efremenko A, Pendse S, Creek M, Osimitz T, Hines R, Hinderliter P, Clewell H, Lake B, Yoon M. Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans. Toxicological Sciences 2019, 173: 86-99. PMID: 31593217, PMCID: PMC6944222, DOI: 10.1093/toxsci/kfz211.Peer-Reviewed Original ResearchConceptsTarget tissue exposureTissue exposurePharmacokinetic modelLiver blood flowLow internal exposureAge-related sensitivityAge-dependent changesEfficient metabolic clearanceIndividual cytochrome P450Human hepatic metabolismAge-related differencesCis-permethrinHepatic metabolismBlood flowMetabolic clearanceCES enzymesHepatic CLintInternal doseIntrinsic clearanceTarget tissuesInternal exposureClearanceCarboxylesterase enzymesCytochrome P450Vivo extrapolation
2018
The Impact of Scaling Factor Variability on Risk-Relevant Pharmacokinetic Outcomes in Children: A Case Study Using Bromodichloromethane (BDCM)
Kenyon E, Lipscomb J, Pegram R, George B, Hines R. The Impact of Scaling Factor Variability on Risk-Relevant Pharmacokinetic Outcomes in Children: A Case Study Using Bromodichloromethane (BDCM). Toxicological Sciences 2018, 167: 347-359. PMID: 30252107, PMCID: PMC10448349, DOI: 10.1093/toxsci/kfy236.Peer-Reviewed Original ResearchConceptsPharmacokinetic outcomesPK outcomesYounger age groupsDose-response studyBDCM concentrationsLarge inter-individual differencesPediatric populationLiver massBody weightAge groupsMicrosomal contentOral exposure routePharmacokinetic modelDose metricsDrink of waterEnzyme ontogenyOutcome variationEarly childhoodAdult findingsInter-individual differencesOutcomesNeonatesExposure routes
2016
Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards
El-Masri H, Kleinstreuer N, Hines R, Adams L, Tal T, Isaacs K, Wetmore B, Tan Y. Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards. Toxicological Sciences 2016, 152: 230-243. PMID: 27208077, PMCID: PMC5009469, DOI: 10.1093/toxsci/kfw082.Peer-Reviewed Original ResearchConceptsPutative adverse outcome pathwayExposure levelsPharmacokinetic modelAdverse outcome pathwaysPotential exposure levelsFetal blood levelsExternal exposure levelsMaternal exposureBlood levelsExposure modelHigh-throughput toxicity screeningVasculogenesis/angiogenesisOutcome pathwaysPBPK modelExposure estimatesChemical dispositionDevelopmental toxicityPotential exposureVivo extrapolationExposureAdulthood stagesToxicityAssaysEnvironmental exposure modelsPregnancy
2009
Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population
Hines R, Sargent D, Autrup H, Birnbaum L, Brent R, Doerrer N, Hubal E, Juberg D, Laurent C, Luebke R, Olejniczak K, Portier C, Slikker W. Approaches for Assessing Risks to Sensitive Populations: Lessons Learned from Evaluating Risks in the Pediatric Population. Toxicological Sciences 2009, 113: 4-26. PMID: 19770482, PMCID: PMC3469276, DOI: 10.1093/toxsci/kfp217.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsBiomarkersChildChild, PreschoolDose-Response Relationship, DrugEnvironmental ExposureEnvironmental MonitoringGenetic Predisposition to DiseaseGovernment RegulationHealth PolicyHumansInfantInfant, NewbornModels, BiologicalPharmacokineticsPublic HealthRisk AssessmentRisk FactorsToxicity Tests
2006
Population-Based Analysis of Methadone Distribution and Metabolism Using an Age-Dependent Physiologically Based Pharmacokinetic Model
Yang F, Tong X, McCarver D, Hines R, Beard D. Population-Based Analysis of Methadone Distribution and Metabolism Using an Age-Dependent Physiologically Based Pharmacokinetic Model. Journal Of Pharmacokinetics And Pharmacodynamics 2006, 33: 485-518. PMID: 16758333, DOI: 10.1007/s10928-006-9018-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAnalgesics, OpioidArea Under CurveBiological AvailabilityChild, PreschoolComputer SimulationHumansHydrogen-Ion ConcentrationInfantInfant, NewbornMaleMethadoneMiddle AgedModels, BiologicalMonte Carlo MethodProtein BindingRegression AnalysisStereoisomerismTissue DistributionConceptsInter-individual variabilityPediatric populationPharmacokinetic modelMethadone kineticsPopulation-based analysisPopulation-based pharmacokineticsMetabolism of methadoneMethadone distributionMethadone metabolismMethadone pharmacokineticsOpioid abstinencePediatric patientsClinical effectsPD relationshipBlood concentrationsPlasma concentrationsLimited pharmacokineticsPharmacodynamic dataOrosomucoid concentrationPK parametersPK dataMethadonePharmacokineticsClearance kineticsPBPK modelModeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene
Nong A, McCarver D, Hines R, Krishnan K. Modeling interchild differences in pharmacokinetics on the basis of subject-specific data on physiology and hepatic CYP2E1 levels: A case study with toluene. Toxicology And Applied Pharmacology 2006, 214: 78-87. PMID: 16464483, DOI: 10.1016/j.taap.2005.12.001.Peer-Reviewed Original ResearchConceptsHepatic CYP2E1 contentCYP2E1 contentLiver volumeHepatic CYP2E1 protein levelsInternal doseHepatic CYP2E1 levelsInterindividual variability factorsPBPK modelVenous blood concentrationsBlood concentration profilesCYP2E1 protein levelsSubgroup of childrenNeonate groupPercentile valuesPpm tolueneBlood concentrationsCYP2E1 levelsHepatic metabolismBody weightLower AUCAge groupsHuman volunteersInterindividual variabilityPharmacokinetic modelIntrinsic clearance