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
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
2008
The ontogeny of drug metabolism enzymes and implications for adverse drug events
Hines R. The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacology & Therapeutics 2008, 118: 250-267. PMID: 18406467, DOI: 10.1016/j.pharmthera.2008.02.005.Peer-Reviewed Original ResearchConceptsAdverse drug eventsDrug eventsDrug metabolism enzymesDME groupPediatric patientsThird trimesterCurrent knowledgeFirst trimesterDrug therapyDrug dispositionPharmacokinetic modelLow levelsEnzyme levelsTrimesterEnzyme expressionGestationSecond groupFetusesMetabolism enzymesBirthPhysiological factorsDevelopmental expression patternsMinimal changesReviewGroup
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 timingThe Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes
Hines R, McCarver D. The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes. Journal Of Pharmacology And Experimental Therapeutics 2002, 300: 355-360. PMID: 11805191, DOI: 10.1124/jpet.300.2.355.Peer-Reviewed Original ResearchThe Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms
McCarver D, Hines R. The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms. Journal Of Pharmacology And Experimental Therapeutics 2002, 300: 361-366. PMID: 11805192, DOI: 10.1124/jpet.300.2.361.Peer-Reviewed Original ResearchConceptsDrug-metabolizing enzyme expressionFetal liverN-acetyltransferase 1 (NAT1) activitiesPhase II conjugation enzymeHuman drug metabolizing enzymesEnzyme expressionDrug metabolizing enzymesPaucity of dataPhase II enzymesCCAAT/enhancer binding protein (C/EBP) familyHepatocyte nuclear factorSecond trimesterAdrenal glandHepatic expressionPostnatal changesNAT1 expressionFetal expressionNuclear factorUDP-glucuronosyltransferasePhase ILiverSulfotransferase isoformsRelated factorsIsoform expression patternLimited data