Arylamine-acetyltransferase 2 genotype-dependent-acetylation of isoniazid in cryopreserved human hepatocytes.
10.1016/j.apsb.2017.05.003
- Author:
Mark A DOLL
1
;
Raúl A SALAZAR-GONZÁLEZ
1
;
Srineil BODDULURI
1
;
David W HEIN
1
Author Information
1. Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
- Publication Type:Journal Article
- Keywords:
Acetylation polymorphism;
Genotype;
Human hepatocytes;
Isoniazid;
N-Acetyltransferase 2;
Phenotype
- From:
Acta Pharmaceutica Sinica B
2017;7(4):517-522
- CountryChina
- Language:English
-
Abstract:
Cryopreserved human hepatocytes were used to investigate the role of arylamine-acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the-acetylation of isoniazid (INH).genotype was determined by Taqman allelic discrimination assay and INH-acetylation was measured by high performance liquid chromatography. INH-acetylation ratesexhibited a robust and highly significant (<0.005) NAT2 phenotype-dependent metabolism.-acetylation rateswere INH concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (= 0.0023 and= 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association betweengenotype and phenotype supports use ofgenotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.
