Pharmacokinetics of isoniazid in children with tuberculosis—A comparative study at two doses

AIM: To compare the pharmacokinetics of isoniazid (INH) at doses 5 and 10 mg/kg/day. METHODS: INH concentrations were estimated by high-performance liquid chromatography in 24 Indian children aged 1 to 15 years on antituberculosis therapy. Blood samples were collected at 0, 2, 4, 6, 8 hours after administration of INH. Patients were randomly given INH at 5 or 10 mg/kg/day and maximum concentrations (Cmax ) and area under the curve (AUC(0-8) ) were determined in each group. The 2-hour concentration of INH was used as Cmax for this study. RESULTS: Mean (standard deviation) Cmax was reached in 2 hours and was 2.68 +/- 1.19 microg/mL in 5 mg/kg/day group and 8.86 +/- 3.94 microg/mL in 10 mg/kg/day group (P < .05). The normal therapeutic range at 2-hour concentrations for INH in adults achieving good clinical response is between 3 and 5 microg/mL. Among 5 mg/kg/day, only 4 (33%) patients had INH concentrations within the 2-hour concentrations therapeutic range whereas in 10 mg/kg/day group, 11 (91%) patients achieved Cmax higher than the 2-hour concentrations therapeutic range and 1 (9%) patient had Cmax within the 2-hour concentrations therapeutic range. The mean AUC(0-8) in 5 mg/kg/day group was 10.04 +/- 6.12 and 35.93 +/- 25.37 microg.h/mL in 10 mg/kg/day group (P = .0001). CONCLUSION: Children on daily INH 10 mg/kg/day have higher AUC and Cmax than the required therapeutic range whereas over 65% of children with daily 5 mg/kg/day INH therapy failed to achieve the optimal therapeutic range.