2019
A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes
Matlock M, Tambe A, Elliott-Higgins J, Hines R, Miller G, Swamidass S. A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes. Chemical Research In Toxicology 2019, 32: 1707-1721. PMID: 31304741, PMCID: PMC6933754, DOI: 10.1021/acs.chemrestox.9b00223.Peer-Reviewed Original ResearchConceptsAge-dependent changesHepatic Drug Metabolizing EnzymesAdverse drug reactionsValproic acid toxicityDrug metabolizing enzymesDrug metabolism enzymesElimination of drugsPediatric patientsPediatric populationMetabolite exposureDrug reactionsClinical dataElevated riskOverall clearanceDrug toxicityFunction of ageDrug safetyFetal periodMetabolizing enzymesDrug metabolismDrug toxicity risksPotential mechanismsAcid toxicityEnzyme expressionDemographic factors
2012
Developmental expression of drug metabolizing enzymes: Impact on disposition in neonates and young children
Hines R. Developmental expression of drug metabolizing enzymes: Impact on disposition in neonates and young children. International Journal Of Pharmaceutics 2012, 452: 3-7. PMID: 22766445, DOI: 10.1016/j.ijpharm.2012.05.079.Peer-Reviewed Original ResearchConceptsPerinatal changesDrug dispositionPediatric drug safetyYoung childrenDrug metabolizing enzymesAge-dependent changesSignificant interindividual variationAdverse eventsPharmacogenetic factorsHepatic drugFunctional genetic variantsDrug safetyDrug efficacyMetabolizing enzymesPharmacokinetic modelInterindividual variationEnzyme ontogenyDrugsEnzyme expressionChildrenClass 3Genetic variantsMajor determinantClass 1Current knowledgeAge‐Dependent Expression of Human Drug‐Metabolizing Enzymes
Hines R. Age‐Dependent Expression of Human Drug‐Metabolizing Enzymes. 2012, 1-33. DOI: 10.1002/9780470921920.edm085.Peer-Reviewed Original Research
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
2006
Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3
Hines R. Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3. Expert Opinion On Drug Metabolism & Toxicology 2006, 2: 41-49. PMID: 16863467, DOI: 10.1517/17425255.2.1.41.Peer-Reviewed Original ResearchConceptsAnimal modelsMost animal modelsHuman fetal liverAdult human liverAdverse reactionsToxicant dispositionTherapeutic efficacyDrug metabolismHuman liverFetal liverToxicant metabolismDrugsEnzyme expressionCytochrome P450-dependent monooxygenasesLiverP450-dependent monooxygenasesFamily membersFMO enzymesRecent studiesMonooxygenases 1FMO3MetabolismExpression patternsExpression
2002
The 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