title: Antituberculosis Drug-Induced Hepatotoxicity in IranianTuberculosis Patients: Role of Isoniazid Metabolic Polymorphism.
abstract: The aim of this study was to determine the association of n-acetyltransferase-2 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Iranian pulmonary tuberculosis patients. Acetylating phenotypes was studied in 50 Iranian pulmonary tuberculosis patients using metabolic ratio of plasma acetyl-Isoniazid to Isoniazid. The association between hepatotoxicity and the n-acetyltransferase-2 phenotype was evaluated by using the chi-square (x(2)) test. The metabolic ratio had a bimodal distribution with an antimode value of 1.0. Based on the metabolic ratio of the mentioned patients, 20 (40%) were slow acetylators and 30 (60%) were fast ones. Hepatotoxicity was manifested in 9 of 20 slow acetylators (45%) and only in 5 of 30 rapid acetylators (16.7%). There was a significant difference in the frequency of hepatotoxicity between the slow and fast acetylators (x(2) = 4.778, and p = 0.03). Sex and age were not found to be risk factors for hepatotoxicity. Our findings show that slow acetylation profile is significantly associated with a higher risk of developing hepatotoxicity due to the anti-TB drugs in Iranian pulmonary tuberculosis patients.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sistanizad
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Azizi
authors.forename: Hosein
authors.initials: H
authors.lastname: Khalili
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Hajiabdolbaghi
authors.forename: Kheirollah
authors.initials: K
authors.lastname: Gholami
authors.forename: Reza
authors.initials: R
authors.lastname: Mahjub
keywords: Antituberculosis; Hepatotoxicity; Isoniazid; Polymorphism; Tuberculosis