Paediatric Tuberculosis Clinic, Department of Paediatrics, B J Wadia Hospital for Children, Mumbai.
Department of Clinical Pharmacology, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India.
Int J Tuberc Lung Dis. 2019 Jan 1;23(1):52-57. doi: 10.5588/ijtld.18.0463. Epub 2018 Dec 20.
To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children.
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) and area under the curve (AUC) were determined. The normal therapeutic range for C is 3-5 μg/ml. An AUC of <10.52 μg•h/ml for INH is low.
The mean C was 8.3 ± 4.28 μg/ml and was attained in 1.22 ± 0.5 h, with a median time to C (T) 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 of respectively 9.87 ± 5.75 μg/ml, 7.62 ± 3.37 μg/ml and 7.21 ± 2.50 μg/ml ( 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 ( 0.29). The mean C in children taking fixed-drug combinations and individual drugs was respectively 9.07 ± 4.67 μg/ml and 7.43 ± 3.71 μg/ml ( 0.26); the mean AUC was respectively 50.48 ± 38.38 μg•h/ml and 41.20 ± 30.52 μg•h/ml ( 0.44). Two children had hepatitis.
Most Indian children had higher than normal INH AUC and C 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.
评估印度儿童每天 10 毫克/公斤异烟肼（INH）的药代动力学。
35 名年龄在 1-15 岁的接受抗结核治疗的儿童每天服用 INH 后 0、1、2、3、6 和 24 小时采集血样，使用液相色谱-串联质谱法估计 INH 水平。测定最大浓度（C）和曲线下面积（AUC）。C 的正常治疗范围为 3-5μg/ml。INH 的 AUC 小于 10.52μg·h/ml 为低。
平均 C 为 8.3±4.28μg/ml，在 1.22±0.5 小时达到，C 的中位数时间（T）为 1 小时。INH 的平均 AUC 为 46.23±34.82μg·h/ml。1-4.9 岁、5-10 岁和>10 岁的儿童平均 C 分别为 9.87±5.75μg/ml、7.62±3.37μg/ml 和 7.21±2.50μg/ml（0.08），平均 AUC 分别为 60.97±49.90μg·h/ml、38.95±22.28μg·h/ml 和 36.09±13.56μg·h/ml（0.29）。服用固定剂量组合和单一药物的儿童的平均 C 分别为 9.07±4.67μg/ml 和 7.43±3.71μg/ml（0.26）；平均 AUC 分别为 50.48±38.38μg·h/ml 和 41.20±30.52μg·h/ml（0.44）。有两名儿童出现肝炎。
大多数印度儿童的 INH AUC 和 C 值高于正常水平。需要根据患者的基因型乙酰化状态和药代动力学毒性分析，确定印度儿童 INH 的理想剂量。
