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
2016
Prediction of Warfarin Dose in Pediatric Patients: An Evaluation of the Predictive Performance of Several Models
Marek E, Momper J, Hines R, Takao C, Gill J, Pravica V, Gaedigk A, Burckart G, Neville K. Prediction of Warfarin Dose in Pediatric Patients: An Evaluation of the Predictive Performance of Several Models. The Journal Of Pediatric Pharmacology And Therapeutics 2016, 21: 224-32. PMID: 27453700, PMCID: PMC4956330, DOI: 10.5863/1551-6776-21.3.224.Peer-Reviewed Original ResearchValidation cohortPediatric patientsStable international normalized ratioInternational normalized ratioStable warfarin dosesFixed-dose approachActual maintenance doseMaintenance doseMaintenance dosesStandard careMulticenter trialWarfarin dosesNormalized ratioSeparate clinical sitesWarfarin doseIndependent cohortClinical sitesCohortPatientsDose prediction modelDose modelDosesProportion of varianceObserved dosesDose
2010
Pharmacogenetic Testing in the Pediatric Epileptic Population
Sander T, Marcuccilli C, Zembles T, Hines R, Lo S, North P. Pharmacogenetic Testing in the Pediatric Epileptic Population. The FASEB Journal 2010, 24: 568.16-568.16. DOI: 10.1096/fasebj.24.1_supplement.568.16.Peer-Reviewed Original ResearchAdverse drug reactionsAntiepileptic drugsSevere adverse drug reactionsABCB1 genetic variantsChronic neurologic disordersFast Real-Time PCR SystemRecurrent unprovoked seizuresAED therapyPediatric patientsUnprovoked seizuresADR riskDrug reactionsPhysician comfortNeurologic disordersEpileptic populationPharmacogenetic testingTherapeutic windowPharmacogenetic testsPatientsTherapeutic treatmentGenotype resultsReal-time PCR systemGenotyping assaysTherapyGenetic variants
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
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 model