Antituberculosis Drug-Induced Hepatotoxicity in Iranian Tuberculosis Patients: Role of Isoniazid Metabolic Polymorphism

作者：Sistanizad Mohammad; Azizi Ebrahim; Khalili Hosein^*; Hajiabdolbaghi Mahboobeh; Gholami Kheirollah; Mahjub Reza

来源：Iranian Journal of Pharmaceutical Research, 2011, 10(3): 633-639.

• Antituberculosis
• Tuberculosis
• Polymorphism
• Isoniazid
• Hepatotoxicity

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.

• 出版日期2011-9