2021
A Rapid Pharmacogenomic Assay to Detect NAT2 Polymorphisms and Guide Isoniazid Dosing for Tuberculosis Treatment.
Verma R, Patil S, Zhang N, Moreira F, Vitorio M, Santos A, Wallace E, Gnanashanmugam D, Persing D, Savic R, Croda J, Andrews J. A Rapid Pharmacogenomic Assay to Detect NAT2 Polymorphisms and Guide Isoniazid Dosing for Tuberculosis Treatment. American Journal Of Respiratory And Critical Care Medicine 2021, 204: 1317-1326. PMID: 34375564, DOI: 10.1164/rccm.202103-0564oc.Peer-Reviewed Original ResearchConceptsPharmacogenomic assaysSparse pharmacokinetic samplingInadequate treatment responseInterindividual pharmacokinetic variabilityAcetylation genotypeIsoniazid clearancePharmacokinetic samplingPulmonary tuberculosisWhole blood samplesIntermediate acetylatorsPharmacokinetic variabilityFast acetylatorsNAT2 polymorphismsAcetylator typeSlow acetylatorsTuberculosis treatmentTreatment responseBlood samplesGeneXpert platformTuberculosis diagnosisVariable drug concentrationsHealthy individualsPersonalized dosingSubstantial incidenceStandardized dosing
2020
Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis
Rens N, Groot C, Goldhaber-Fiebert J, Croda J, Andrews J. Cost-effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis. Clinical Infectious Diseases 2020, 71: 3136-3143. PMID: 31905381, PMCID: PMC7819527, DOI: 10.1093/cid/ciz1212.Peer-Reviewed Original ResearchMeSH KeywordsArylamine N-AcetyltransferaseBrazilCost-Benefit AnalysisHumansIndiaIsoniazidPharmacogeneticsQuality-Adjusted Life YearsSouth AfricaTuberculosisConceptsDrug-susceptible tuberculosisIncremental cost-effectiveness ratioSlow NAT2 acetylatorsWeight-based dosingOne-way sensitivity analysesCost-effectiveness ratioN-acetyltransferase 2 geneEffectiveness of drugsProbabilistic sensitivity analysesPotential clinical impactGeneXpert testActive tuberculosisNAT2 acetylatorsTreatment failurePharmacokinetic variabilityRapid acetylatorsTuberculosis treatmentClinical impactMAIN OUTCOMEPharmacogenomic testsHealth outcomesIsoniazid toxicityInterindividual variabilityPatientsTuberculosis
2016
Factors associated with anti-TB drug-induced hepatotoxicity and genetic polymorphisms in indigenous and non-indigenous populations in Brazil
Heinrich M, Zembrzuski V, Ota M, Sacchi F, Teixeira R, Acero P, Cunha G, Souza-Santos R, Croda J, Basta P. Factors associated with anti-TB drug-induced hepatotoxicity and genetic polymorphisms in indigenous and non-indigenous populations in Brazil. Tuberculosis 2016, 101: 15-24. PMID: 27865386, DOI: 10.1016/j.tube.2016.07.006.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntitubercular AgentsArylamine N-AcetyltransferaseBrazilChemical and Drug Induced Liver InjuryChildChild, PreschoolCross-Sectional StudiesCytochrome P-450 CYP2E1FemaleGenetic Predisposition to DiseaseGenotypeGlutathione TransferaseHumansIncidenceInfantLongitudinal StudiesMaleMiddle AgedPolymorphism, Single NucleotideTuberculosis, PulmonaryYoung AdultConceptsIncidence of hepatotoxicityAdverse drug reactionsIndigenous patientsAnti-TB drug-induced hepatotoxicityNon-conditional logistic regressionClinical-epidemiological factorsClinical-epidemiological variablesNon-Indigenous patientsGenetic polymorphismsRisk of hepatotoxicityDrug-induced hepatotoxicityPolymorphisms of CYP2E1Anti-tuberculosis drugsAcetylation profileTB patientsSerum levelsDrug reactionsGSTM1 polymorphismOdds ratioLiver enzymesNon-Indigenous populationsTherapeutic schemesPharmacogenetic analysisBetter outcomesPatients