University of Colorado Denver, Aurora, Colorado, USA.
Ther Drug Monit. 2012 Aug;34(4):446-51. doi: 10.1097/FTD.0b013e31825c4bc3.
There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing.
Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥3 mg/L, and area under the curve (AUC0-24) ≥10.52 mg·h/L.
In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg·kg·d, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg·h/L, respectively, and mean (±SD) half-lives were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of the NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg·kg·d, 99% of infants aged 3-24 months have an INH Cmax ≥3 mg/L, and 98% have an INH AUC0-24 ≥10.52 mg·h/L.
INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥3 mg/L and AUC0-24 values ≥10.52 mg·h/L.
关于异烟肼（INH）在婴儿和幼儿中的药代动力学数据有限，因此在剂量方面存在不确定性。
从南非接受 HIV 围生期暴露的 3-24 个月大的婴儿中获得 INH 药代动力学数据，这些婴儿接受的 INH 剂量为 10-20mg·kg·d 口服，用于预防结核分枝杆菌。使用群体药代动力学方法描述 INH 药代动力学参数。进行剂量模拟，根据 N-乙酰转移酶 2 酶（NAT2）基因型、年龄、最大浓度（Cmax）≥3mg/L 和曲线下面积（AUC0-24）≥10.52mg·h/L 评估儿童的基于体重的 INH 剂量。
在 151 名接受平均 INH 剂量为 14.5mg·kg·d 的婴儿中（53%为女性，48%为 HIV 阳性），3、6 和 23 个月时的平均（±SD）Cmax 分别为 10.0（3.5）、8.6（2.6）和 9.3（3.8）mg/L，平均（±SD）AUC0-24 分别为 53.6（26.8）、42（19.9）和 44（30.7）mg·h/L，平均（±SD）半衰期分别为 2.1（0.7）、1.9（0.6）和 1.8（0.9）小时。早在 3 个月时，就明显出现了作为 NAT2 基因型函数的 INH 口服清除率的三模态。INH 耐受性良好。在平均 INH 剂量为 14.5mg·kg·d 的情况下，99%的 3-24 个月大的婴儿 INH Cmax≥3mg/L，98%的婴儿 INH AUC0-24≥10.52mg·h/L。
平均剂量为 14.5mg/kg 的 INH 每日一次口服在婴儿中耐受性良好，达到 INH Cmax 值≥3mg/L 和 AUC0-24 值≥10.52mg·h/L。
