[Isoniazid phenotype in a group of Tunisian patients. About 620 patients]

Isoniazid is a first line antituberculosis drug metabolized mainly in the liver by the Nacetyltransferase2. There are differences between individuals in acetylation metabolism. Subjects are thereby characterized as being rapid or slow acetylation. The purpose is to study the distribution pattern of acetylation in patients with tuberculosis followed up the teaching Hospital of La Rabta. The determination of acetylator phenotype was carried out on 620 tuberculosis patients during a period of 12 years. There were 483 men and 137 women with a median age of 40.3 years. The test was investigated before drug regimen administration at the dose of 5 mg/kg. A blood sample was taken three hours after the first administration. The determination of acetylation profile was worked out by Vivien hypothesis. In our population 391 were low and 229 were fast acetylators. The median dose recommended within the test was 3.04 mg/kg/day. 56% of our patients were initially receiving high dose of isoniazid. An increase in serum transaminase was initially observed in 60 patients among whom 47 slow acetylators. After dose adaptation, 53 patients had improved their biological abnormalities. The majority of Tunisian population seem to belong to slow acetylators modal. The frequency of hepatotoxicity suggests reducing the recommended dose of isoniazid from 5 to 3 mg/kg/day