Pharmacokinetics of isoniazid in Indian children with tuberculosis on daily treatment

Objective To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children. Methods INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1-15 years on daily anti-tuberculosis treatment. Blood samples were collected 0, 1, 2, 3, 6 and 24 h after INH administration. The maximum concentration (C max ) and area under the curve (AUC 0-24 ) were determined. The normal therapeutic range for C max is 3-5 μg/ml. An AUC of Results The mean C max was 8.3 ± 4.28 μg/ml and was attained in 1.22 ± 0.5 h, with a median time to C max (T max ) of 1 h. The mean AUC for INH was 46.23 ± 34.82 μg•h/ml. Children aged 1-4.9 years, 5-10 years and >10 years had a mean C max of respectively 9.87 ± 5.75 μg/ml, 7.62 ± 3.37 μg/ml and 7.21 ± 2.50 μg/ml ( P = 0.08) and a mean AUC of respectively 60.97 ± 49.90 μg•h/ml, 38.95 ± 22.28 μg•h/ml and 36.09 ± 13.56 μg•h/ml ( P = 0.29). The mean C max in children taking fixed-drug combinations and individual drugs was respectively 9.07 ± 4.67 μg/ml and 7.43 ± 3.71 μg/ml ( P = 0.26); the mean AUC was respectively 50.48 ± 38.38 μg•h/ml and 41.20 ± 30.52 μg•h/ml ( P = 0.44). Two children had hepatitis. Conclusion Most Indian children had higher than normal INH AUC and C max values . It is necessary to determine the ideal dose of INH in Indian children using the genotypic acetylator status of the patients and pharmacokinetic toxicity analysis.