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
Expression 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 rangeMonthsAge-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
2015
Ontogeny of plasma proteins, albumin and binding of diazepam, cyclosporine, and deltamethrin
Sethi P, White C, Cummings B, Hines R, Muralidhara S, Bruckner J. Ontogeny of plasma proteins, albumin and binding of diazepam, cyclosporine, and deltamethrin. Pediatric Research 2015, 79: 409-415. PMID: 26571224, DOI: 10.1038/pr.2015.237.Peer-Reviewed Original ResearchConceptsTotal proteinBinding of diazepamUnbound diazepamAlbumin levelsStandard dosesPlasma levelsDrugs/chemicalsPediatric databasePlasma bindingAge groupsMaturational changesAdult levelsCyclosporineDiazepamPlasma albuminThree- to fourfoldPlasma samplesFree drugNeonatesPlasma proteinsPyrethroid insecticidesAge bracketDrugsAlbuminRisk
2014
Human Hepatic UGT2B15 Developmental Expression
Divakaran K, Hines R, McCarver D. Human Hepatic UGT2B15 Developmental Expression. Toxicological Sciences 2014, 141: 292-299. PMID: 24980262, PMCID: PMC4271124, DOI: 10.1093/toxsci/kfu126.Peer-Reviewed Original ResearchConceptsUGT2B15 expressionAge groupsHuman hepatic microsomesLate fetal lifeFunctional single nucleotide polymorphismsFetal contentMale genderFetal lifeLate gestationPostnatal samplesLower clearanceOlder individualsWeeks ageHepatic microsomesProtein expressionSingle nucleotide polymorphismsLatter groupImportant drugsMature valuesBisphenol ADevelopmental expressionExpression changesNucleotide polymorphismsGreater rateGroup
2009
Human 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 dosesModeling 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
2003
Human Hepatic CYP2E1 Expression during Development
Johnsrud E, Koukouritaki S, Divakaran K, Brunengraber L, Hines R, McCarver D. Human Hepatic CYP2E1 Expression during Development. Journal Of Pharmacology And Experimental Therapeutics 2003, 307: 402-407. DOI: 10.1124/jpet.103.053124.Peer-Reviewed Original ResearchConceptsPostnatal ageDays of ageNeonatal samplesOlder infantsCYP2E1 contentHepatic CYP2E1 expressionDays postnatal ageHuman hepatic microsomesHuman fetal liverInfants 31CYP2E1 protein contentGestational ageThird trimesterPostnatal dataGreat intersubject variationCYP2E1 expressionCYP2E1 substratesAge groupsFetal samplesCYP2E1Hepatic microsomesFetal liverInfantsYoung adultsIntersubject variationHuman hepatic CYP2E1 expression during development.
Johnsrud E, Koukouritaki S, Divakaran K, Brunengraber L, Hines R, McCarver D. Human hepatic CYP2E1 expression during development. Journal Of Pharmacology And Experimental Therapeutics 2003, 307: 402-7. PMID: 14500779, DOI: 10.1124/jpet.102.053124.Peer-Reviewed Original ResearchConceptsPostnatal ageNeonatal samplesThird trimesterOlder infantsIncreasing gestational ageDays postnatal ageHuman fetal liverCYP2E1 contentDays of ageImmunodetectable CYP2E1Gestational ageHuman hepatic microsomesSecond-trimesterPostnatal dataFetal liverFetal samplesHepatic CYP2E1 expressionDecreased clearanceInfantsCYP2E1 expressionIntersubject variationCYP2E1CYP2E1 protein contentAge groupsCYP2E1 substrates