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
2017
Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages
Song G, Sun X, Hines R, McCarver D, Lake B, Osimitz T, Creek M, Clewell H, Yoon M. Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages. Drug Metabolism And Disposition 2017, 45: dmd.116.074583. PMID: 28228413, DOI: 10.1124/dmd.116.074583.Peer-Reviewed Original ResearchConceptsCYP2C8 expressionOntogeny dataMonths postnatal ageProtein levelsLiver microsomal samplesAge-dependent expressionMultiple cytochrome P450Weeks' gestationPostnatal agePostnatal dayYoung infantsPostnatal samplesFetal samplesMicrosomal samplesCYP1A2 expressionQuantitative Western blottingPyrethroid metabolismCYP2C8Western blottingHealth risk assessmentHuman health risk assessmentRisk assessmentAgeCarboxylesterase enzymesCytochrome P450
2016
Age-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
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
2008
Developmental Changes in Human Liver CYP2D6 Expression
Stevens J, Marsh S, Zaya M, Regina K, Divakaran K, Le M, Hines R. Developmental Changes in Human Liver CYP2D6 Expression. Drug Metabolism And Disposition 2008, 36: 1587-1593. PMID: 18474679, DOI: 10.1124/dmd.108.021873.Peer-Reviewed Original Research
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 doses
2003
Developmental Expression of the Major Human Hepatic CYP3A Enzymes
Stevens J, Hines R, Gu C, Koukouritaki S, Manro J, Tandler P, Zaya M. Developmental Expression of the Major Human Hepatic CYP3A Enzymes. Journal Of Pharmacology And Experimental Therapeutics 2003, 307: 573-582. PMID: 12975492, DOI: 10.1124/jpet.103.054841.Peer-Reviewed Original Research
2002
Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression
Koukouritaki S, Simpson P, Yeung C, Rettie A, Hines R. Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression. Pediatric Research 2002, 51: 236-243. PMID: 11809920, DOI: 10.1203/00006450-200202000-00018.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenasesExpression patternsSpecies-specific expression patternsFMO3 expressionTemporal expression patternsMajor adult isoformFMO genesPotential control mechanismsDevelopmental expressionProtein levelsAdult isoformsWestern blottingExpressionEmbryosNumerous therapeuticsIsoformsMonooxygenases 1Most individualsFMO3Microsomal fractionHuman liver samplesIntermediate levelsControl mechanismsGenesPrecise timing
1997
Variation in Induction of Human Placental CYP2E1: Possible Role in Susceptibility to Fetal Alcohol Syndrome?
Rasheed A, Hines R, McCarver-May D. Variation in Induction of Human Placental CYP2E1: Possible Role in Susceptibility to Fetal Alcohol Syndrome? Toxicology And Applied Pharmacology 1997, 144: 396-400. PMID: 9194424, DOI: 10.1006/taap.1997.8152.Peer-Reviewed Original ResearchConceptsFetal alcohol syndromeAlcohol syndromeIntersubject variationHeavy drinking womenSmall birth weightAbsolute alcohol intakeWestern blot analysisBirth lengthAlcohol intakeDrinking womenHepatic CYP2E1Birth weightTerm placentaHeavy drinkersAlcohol metabolismCYP2E1Placental microsomesHuman placentaHeavy drinkingPlacentaTime pointsPotential mechanismsEnvironmental agentsWomenPregnancy
1986
The molecular biology of the polycyclic aromatic hydrocarbon inducible cytochrome P‐450; the past is prologue
Iversen P, Hines R, Bresnick E. The molecular biology of the polycyclic aromatic hydrocarbon inducible cytochrome P‐450; the past is prologue. BioEssays 1986, 4: 15-19. PMID: 3790107, DOI: 10.1002/bies.950040105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytochrome P-450 Enzyme SystemEnzyme InductionGenesMicrosomes, LiverPolycyclic CompoundsRatsConceptsRegulation of expressionEnzyme systemUbiquitous familySubstrate specificityGene expressionMultiple isozymesMolecular biologyCytochrome PToxic lesionsExogenous compoundsOxidative metabolismMechanisms of metabolismExpressionInducible cytochrome PIsozymesComplete understandingMetabolismBiochemical pharmacologyOrganismsBiologySpeciesRegulationWide varietyCascadeCurrent notions
1984
Demonstration of microsomal oxygenation of the benzo ring of 6-nitrobenzo[a]pyrene by thin-layer chromatography
Raha C, Hines R, Bresnick E. Demonstration of microsomal oxygenation of the benzo ring of 6-nitrobenzo[a]pyrene by thin-layer chromatography. Journal Of Chromatography 1984, 291: 231-239. PMID: 6539786, DOI: 10.1016/s0021-9673(00)95024-6.Peer-Reviewed Original Research
1981
The oxidation of hydrazine derivatives catalyzed by the purified liver microsomal FAD-containing monooxygenase.
Prough R, Freeman P, Hines R. The oxidation of hydrazine derivatives catalyzed by the purified liver microsomal FAD-containing monooxygenase. Journal Of Biological Chemistry 1981, 256: 4178-4184. PMID: 7217078, DOI: 10.1016/s0021-9258(19)69416-0.Peer-Reviewed Original Research
1980
The characterization of an inhibitory complex formed with cytochrome P-450 and a metabolite of 1,1-disubstituted hydrazines.
Hines R, Prough R. The characterization of an inhibitory complex formed with cytochrome P-450 and a metabolite of 1,1-disubstituted hydrazines. Journal Of Pharmacology And Experimental Therapeutics 1980, 214: 80-6. PMID: 7391974.Peer-Reviewed Original Research