Pharmacokinetics of isoniazid in Indian children with tuberculosis on daily treatment.

<h2>OBJECTIVE:</h2>To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children.<h2>METHODS:</h2>INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1&ndash;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 (Cmax ) and area under the curve (AUC0&ndash;24 ) were determined. The normal therapeutic range for Cmax is 3&ndash;5 &mu;g/ml. An AUC of &lt;10.52 &mu;g&bull;h/ml for INH is low.<h2>RESULTS:</h2>The mean Cmax was 8.3 &plusmn; 4.28 &mu;g/ml and was attained in 1.22 &plusmn; 0.5 h, with a median time to Cmax (Tmax ) of 1 h. The mean AUC for INH was 46.23 &plusmn; 34.82 &mu;g&bull;h/ml. Children aged 1&ndash;4.9 years, 5&ndash;10 years and &gt;10 years had a mean Cmax of respectively 9.87 &plusmn; 5.75 &mu;g/ml, 7.62 &plusmn; 3.37 &mu;g/ml and 7.21 &plusmn; 2.50 &mu;g/ml (<italic>P &equals;</italic> 0.08) and a mean AUC of respectively 60.97 &plusmn; 49.90 &mu;g&bull;h/ml, 38.95 &plusmn; 22.28 &mu;g&bull;h/ml and 36.09 &plusmn; 13.56 &mu;g&bull;h/ml (<italic>P &equals;</italic> 0.29). The mean Cmax in children taking fixed-drug combinations and individual drugs was respectively 9.07 &plusmn; 4.67 &mu;g/ml and 7.43 &plusmn; 3.71 &mu;g/ml (<italic>P &equals;</italic> 0.26); the mean AUC was respectively 50.48 &plusmn; 38.38 &mu;g&bull;h/ml and 41.20 &plusmn; 30.52 &mu;g&bull;h/ml (<italic>P &equals;</italic> 0.44). Two children had hepatitis.<h2>CONCLUSION:</h2>Most Indian children had higher than normal INH AUC and Cmax values<italic>.</italic> 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.