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
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 modelsPregnancyExpression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver
Thomson M, Hines R, Schuetz E, Meibohm B. Expression Patterns of Organic Anion Transporting Polypeptides 1B1 and 1B3 Protein in Human Pediatric Liver. Drug Metabolism And Disposition 2016, 44: 999-1004. PMID: 27098745, PMCID: PMC4931892, DOI: 10.1124/dmd.115.069252.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgingChildChild, PreschoolFemaleGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGlycosylationHumansInfantInfant, NewbornLiver-Specific Organic Anion Transporter 1MaleProtein Processing, Post-TranslationalSolute Carrier Organic Anion Transporter Family Member 1B3ConceptsYears of ageOrganic anion transporting polypeptide (OATP) 1B1Relative protein expressionAge groupsProtein expressionDrug disposition pathwaysMonths of ageDrug-metabolizing enzymesHigh interindividual variabilityStudied age groupsPolypeptide 1B1Appropriate pharmacotherapyPediatric liverChildren 6Children 2Liver specimensInterindividual variabilityFirst monthDrug transportersWestern blottingDisposition pathwaysPreadolescent periodHigh expressionAge rangeMonthsRole of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny
Giebel N, Shadley J, McCarver D, Dorko K, Gramignoli R, Strom S, Yan K, Simpson P, Hines R. Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny. Drug Metabolism And Disposition 2016, 44: 1027-1037. PMID: 26921389, PMCID: PMC4931893, DOI: 10.1124/dmd.116.069344.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBinding SitesChildChild, PreschoolChromatinChromatin Assembly and DisassemblyCytochrome P-450 CYP3AGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGestational AgeHepatocytesHistonesHumansInfantLiverMiddle AgedNucleic Acid ConformationPromoter Regions, GeneticProtein ConformationStructure-Activity RelationshipTranscription, GeneticAge-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny
Hines R, Simpson P, McCarver D. Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny. Drug Metabolism And Disposition 2016, 44: 959-966. PMID: 26825642, DOI: 10.1124/dmd.115.068957.Peer-Reviewed Original ResearchConceptsHepatic carboxylesterase 1Weeks of ageCarboxylesterase 1CES2 expressionAge groupsYounger age groupsCES1 expressionLiver diseaseAdverse outcomesMetabolic clearancePmol/Older groupOlder individualsWestern blottingLiver samplesWeeksEnvironmental chemicalsPostnatal ontogenyMicrosomal proteinMedian valueAgeCytosolic fractionGroupExpressionSubjects
2012
Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes
Sharma S, Ellis E, Gramignoli R, Dorko K, Tahan V, Hansel M, Mattison D, Caritis S, Hines R, Venkataramanan R, Strom S. Hepatobiliary Disposition of 17-OHPC and Taurocholate in Fetal Human Hepatocytes: A Comparison with Adult Human Hepatocytes. Drug Metabolism And Disposition 2012, 41: 296-304. PMID: 23129211, PMCID: PMC3558857, DOI: 10.1124/dmd.112.044891.Peer-Reviewed Original ResearchMeSH Keywords17 alpha-Hydroxyprogesterone CaproateAdultAge FactorsAgedBiological TransportCells, CulturedCold TemperatureCyclosporineFemaleGestational AgeHepatocytesHumansHydroxyprogesteronesKineticsMaleMembrane Transport ProteinsMiddle AgedMultidrug Resistance-Associated Protein 2RifampinRNA, MessengerTaurocholic AcidVerapamilYoung AdultConceptsHuman hepatocytesFetal human hepatocytesFetal human liverConcentration-dependent inhibitionAdult human hepatocytesBile acid transporterFetal circulationPlacental barrierRecurrent miscarriageSpontaneous abortionProgesterone metabolitesTaurocholate effluxAdult hepatocytesTherapeutic levelsLower mRNA levelsHepatobiliary dispositionHepatic transportersActivity of transportersActive efflux mechanismHuman liverHuman fetalAdverse effectsRole of transportersEfflux mechanismMRNA levels
2011
Prenatal and Postnatal Expression of Glutathione Transferase ζ 1 in Human Liver and the Roles of Haplotype and Subject Age in Determining Activity with Dichloroacetate
Li W, Gu Y, James M, Hines R, Simpson P, Langaee T, Stacpoole P. Prenatal and Postnatal Expression of Glutathione Transferase ζ 1 in Human Liver and the Roles of Haplotype and Subject Age in Determining Activity with Dichloroacetate. Drug Metabolism And Disposition 2011, 40: 232-239. PMID: 22028318, PMCID: PMC3263939, DOI: 10.1124/dmd.111.041533.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAmino Acid SubstitutionAntineoplastic AgentsChildCytoplasmDichloroacetic AcidDrugs, InvestigationalFemaleGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicGlutathione TransferaseHalogenationHumansLiverMaleMiddle AgedMitochondria, LiverPolymorphism, Single NucleotideSubstrate SpecificityYoung AdultConceptsGSTZ1 activityHuman liverProtein expressionAge 74 yearsInfluence of haplotypeAge 7 yearsAge-dependent mannerAge-related increaseRole of haplotypesWeeks' gestationHuman liver developmentNeonatal onsetAge-related differencesLactic acidosisInvestigational drugsSolid tumorsGSTZ1 protein expressionPostnatal expressionSubject ageLevel of expressionFetal liverLiverGSTZ1 expressionExpression levelsTyrosine catabolism
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 TestsHuman hepatic CYP2B6 developmental expression: The impact of age and genotype
Croom E, Stevens J, Hines R, Wallace A, Hodgson E. Human hepatic CYP2B6 developmental expression: The impact of age and genotype. Biochemical Pharmacology 2009, 78: 184-190. PMID: 19464434, DOI: 10.1016/j.bcp.2009.03.029.Peer-Reviewed Original ResearchConceptsYears of ageMedian ageCYP2B6 expressionCYP2B6 levelsProtein levelsSemi-quantitative Western blottingImpact of ageWeeks' gestationNeonatal periodCYP2B6 protein levelsDonor ageCYP3A7 activityPostnatal dayLiver bankAge groupsFetal samplesAdult levelsPediatric samplesWestern blottingCYP2B6 proteinToxicant metabolismAgeSignificant inductionPercentage of samplesPossible role
2006
Epirubicin Glucuronidation and UGT2B7 Developmental Expression
Zaya M, Hines R, Stevens J. Epirubicin Glucuronidation and UGT2B7 Developmental Expression. Drug Metabolism And Disposition 2006, 34: 2097-2101. PMID: 16985101, DOI: 10.1124/dmd.106.011387.Peer-Reviewed Original ResearchConceptsPediatric age categoriesPediatric age groupAge categoriesAge groupsLiver microsomesChildhood malignant diseaseMetabolism of epirubicinUse of epirubicinTreatment of adultsYears of ageMonths of ageAge-related changesPediatric patientsAdult age categoriesPostnatal ageCardiac toxicityMalignant diseaseUGT2B7 activityNeonatal samplesPreclinical evaluationUGT2B7 expressionGlucuronidation activityAdult groupGlucuronidationEquivalent dosesPopulation-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
2005
Developmental Expression of Aryl, Estrogen, and Hydroxysteroid Sulfotransferases in Pre- and Postnatal Human Liver
Duanmu Z, Weckle A, Koukouritaki S, Hines R, Falany J, Falany C, Kocarek T, Runge-Morris M. Developmental Expression of Aryl, Estrogen, and Hydroxysteroid Sulfotransferases in Pre- and Postnatal Human Liver. Journal Of Pharmacology And Experimental Therapeutics 2005, 316: 1310-1317. PMID: 16339912, DOI: 10.1124/jpet.105.093633.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsArylsulfotransferaseBlotting, WesternFemaleFetusHumansInfant, NewbornLiverMaleSulfotransferasesConceptsHuman liver cytosolImmunoreactive protein levelsHuman liverSULT2A1 expressionPostnatal liver samplesProtein levelsLiver cytosolPostnatal human developmentAdult human liverSemiquantitative Western blot analysisWestern blot analysisThird trimesterPostnatal ageEarly gestationEstrogen inactivationSulfotransferase expressionPostnatal lifeInterindividual variabilityPrenatal periodMale liverDifferent developmental profilesSULT1A1 expressionGestationLiverHydroxysteroid sulfotransferases
2000
Developmental regulation of the L-type calcium channel α1C subunit expression in heart
Leu L, O'Hara D, Cala S, Poornima I, Hines R, Marsh J. Developmental regulation of the L-type calcium channel α1C subunit expression in heart. Molecular And Cellular Biochemistry 2000, 205: 101-109. PMID: 10821427, DOI: 10.1023/a:1007013900827.Peer-Reviewed Original ResearchConceptsRNase protection assaysProtection assaysNorthern analysisΑ1C subunitSize of proteinsAlternative splicingAbundance of mRNADevelopmental regulationSmaller transcriptTranscript sizeNative proteinKD proteinMolecular massDevelopmental stagesProteinSubunitsAdult ventriclesTranscriptsPostnatal developmentAbundanceExpressionSubunit expressionCalcium channel propertiesChannel propertiesReceptor message