N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis.
A K Hemanth Kumar,K Ramesh,T Kannan,V. Sudha,Hemalatha Haribabu,J Lavanya,Soumya Swaminathan,Geetha Ramachandran +7 more
TLDR
Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators, and two-hour INH concentrations differed significantly among the three genotypes.Abstract:
Background & objectives: Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH) This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes Methods: Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes Plasma INH was determined by high-performance liquid chromatography Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method Results: Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively The median two-hour INH concentrations in slow, intermediate and fast acetylators were 102, 81 and 41 μg/ml, respectively The differences in INH concentrations among the three genotypes were significant (P Interpretation & conclusions: Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators Two-hour INH concentrations differed significantly among the three genotypesread more
Citations
More filters
Journal ArticleDOI
Current research toward optimizing dosing of first-line antituberculosis treatment.
Helen McIlleron,Maxwell Chirehwa +1 more
TL;DR: Based on population pharmacokinetic models and the weight, height, and sex distributions in a large data base of African tuberculosis patients, a proposed simplified weight-based doses of the available fixed dose combination (FDC) for adults with drug susceptible tuberculosis are proposed.
Journal ArticleDOI
Sexual Dimorphism in Drug Metabolism and Pharmacokinetics
Askhi M Valodara,Kaid Johar +1 more
TL;DR: Sex and gender-based differences in the metabolism of drugs exist at various levels and it may be due to the genomic and non-genomic action of sex hormones.
Journal ArticleDOI
Population Pharmacokinetic Properties of Antituberculosis Drugs in Vietnamese Children with Tuberculous Meningitis.
Navarat Panjasawatwong,Thanaporn Wattanakul,Thanaporn Wattanakul,Richard M. Hoglund,Richard M. Hoglund,Nguyen Duc Bang,Thomas Pouplin,Thomas Pouplin,Wichit Nosoongnoen,Vi Nguyen Ngo,Jeremy N. Day,Joel Tarning,Joel Tarning +12 more
TL;DR: Investigation of the pharmacokinetic properties of isoniazid, rifampin, pyrazinamide, and ethambutol in Vietnamese children with TBM suggested higher doses of rifampsin could be considered, but further studies are needed to establish the safety and efficacy of increased dosing.
Journal ArticleDOI
Analytical and Omics-Based Advances in the Study of Drug-Induced Liver Injury.
TL;DR: In this paper, the authors discuss the analytical techniques that can be applied to characterise and investigate the biological mechanisms of DILI and potential predictive biomarkers, including genomics, transcriptomics, proteomics, and metabolomics.
Journal ArticleDOI
Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers.
S. R. Bakshi,Manmeet Kaur,Nitin Saini,A A Mir,A A Mir,Ajay Duseja,Saroj K. Sinha,Shefali Khanna Sharma +7 more
TL;DR: In this article, the importance of microRNAs 122 and 192 in the detection of drug-induced liver damage was assessed. But the authors did not consider the effect of microRNA on the development of the disease.
References
More filters
Journal ArticleDOI
Therapeutic drug monitoring in the treatment of tuberculosis: an update
TL;DR: Therapeutic drug monitoring (TDM) remains a standard clinical technique for using plasma drug concentrations to determine dose, and under ‘real–life’ circumstances is the best available tool for sorting out these multi-drug interactions, and for providing the patient safe and adequate doses.
Journal ArticleDOI
NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: A randomized controlled trial for pharmacogenetics-based therapy
Junichi Azuma,Masako Ohno,Masako Ohno,Ryuji Kubota,Soichiro Yokota,Takayuki Nagai,Kazunari Tsuyuguchi,Yasuhisa Okuda,Tetsuya Takashima,Sayaka Kamimura,Yasushi Fujio,Ichiro Kawase +11 more
TL;DR: Results clearly indicate a great potential of the NAT2 genotype-guided dosing stratification of isoniazid in chemotherapy for tuberculosis.
Journal ArticleDOI
Should We Use N-Acetyltransferase Type 2 Genotyping To Personalize Isoniazid Doses?
Martina Kinzig-Schippers,Dorota Tomalik-Scharte,Alexander Jetter,Bernhard Scheidel,Verena Jakob,Michael Rodamer,Ingolf Cascorbi,Oxana Doroshyenko,Fritz Sörgel,Uwe Fuhr +9 more
TL;DR: Assessment of individual isoniazid exposure based on NAT2 genotype to predict a personalized therapeutic dose found that current standard doses presumably appropriate for patients with one high-activity NAT2 allele may be decreased or increased by approximately 50% for Patients with no or two such alleles, respectively.
Journal ArticleDOI
Pharmacokinetics of isoniazid metabolism in man.
TL;DR: Detailed pharmacokinetic studies undertaken on a slow and a rapid acetylator of isoniazid enabled approximate first-order rate constants to be calculated for the metabolic processes involved in the conversion of isonicotinic acid to acetylisoniazid, isonicotinylglycine, monoacetylHydrazine, and diacetylhydrazine and their excretion in the urine.
Journal ArticleDOI
NAT2 polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury: a meta-analysis.
TL;DR: This meta-analysis showed that tuberculosis patients with slow acetylators had a higher risk of ATLI than other acetylator patients, and screening of patients for the NAT2 genetic polymorphisms will be useful for the clinical prediction and prevention of AtLI.