Determination of the acetylator phenotype in Moroccan tuberculosis patients using isoniazid as metabolic probe

Abstract

A large interindividual variability in drug acetylation is associated with genetic polymorphism of the polymorphic Type 2 N-acetyltransferase (NAT2), and an important interethnic difference has been frequently observed. However, few data on this polymorphism in the Moroccan population are available. In the present study the acetylator phenotype in 89 Moroccan patients with tuberculosis has been determined using isoniazid (INH) as metabolic probe. The subjects (69 women and 20 men between 18 and 77) were each given a 5 mg/kg oral dose of INH. Plasma concentration of INH and its metabolite, acetylisoniazid (ac.INH), were measured by high-performance liquid chromatography at 3 hours post dose. The plasma level ratio of acetylisoniazid to isoniazid (Rm), and the plasma level of acetylisoniazid as a percentage (%ac.INH) were used to express the activity of the polymorphic NAT2. The distribution of these 2 parameters in the studied population was clearly bimodal resulting in 2 distinct groups: slow acetylators (Rm < or = 0.84, %ac.INH < or = 45.64%), and fast acetylators (Rm > or = 1.29, %ac.INH > or = 56.26%) who accounted respectively for 61.8% and 38.2% of the population. The 2 approaches used showed a complete concordance.