Isoniazid exposures and acetylator status in Indonesian tuberculous meningitis patients.

Abstract

The effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life <130 min) or slow (half-life >130 min) acetylators. Slow acetylators had higher AUC(0-24,) C(max) and CSF concentrations than fast acetylators (GM AUC(0-24) 25.5 vs 10.6 mg/L*h, p < 0.001); plasma C(max) 5.5 vs 3.6 mg/L, p = 0.023; CSF concentration 1.9 vs 1.1 mg/L, p = 0.008). Higher isoniazid doses may benefit fast acetylators in TBM.