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 ResearchConceptsDrug-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