Isoniazid Therapeutic Drug Monitoring in Tunisian Patients With Tuberculosis

Abstract

A regular therapeutic drug monitoring (TDM) of isoniazid could be useful to predict the acetylation profile and to prescribe doses associated with optimal efficacy and safety. We aimed to assess the usefulness of isoniazid TDM in the Tunisian population, to describe the acetylation profile distribution in this population, and to investigate the influence of certain parameters on acetylation phenotype. We performed a retrospective study including Tunisian patients with tuberculosis underwent an isoniazid TDM. Isoniazid concentrations were measured 3 hours after drug intake (C3). Subsequent isoniazid doses were adjusted to maintain the C3 within the recommended target (1‐2 µg/mL). Patients were qualified as slow acetylators (SAs) or rapid acetylators (RAs) according to their acetylation index. Among the 255 patients, 58% were SAs and 42% were RAs. Of all patients, only 30.6% had a C3 value within the target range. A dose adjustment has been performed for patients with C3 outside the target range. C3 was controlled in 77 patients. It became within the target range in 39 patients (50.6%). The median recommended isoniazid weight doses for SAs and RAs were 2.1 ± 0.7 mg/kg and 4.2 ± 1.4 mg/kg, respectively. The multivariate analysis showed that body weight, C3, and C3/isoniazid dose were found to be significantly different between the 2 acetylation groups. In the pediatric group, only 9 had a C3 value within the target range, and all of them were RAs. The irrevocable interest of isoniazid TDM has been shown in Tunisian patients with tuberculosis, in both adult and pediatric patients, as isoniazid demonstrates an unpredictable pharmacokinetic profile.