A limited sampling strategy (LSS) to estimate the exposure to isoniazid was developed considering N-acetyltransferase 2 (NAT2) genotypes in Korean patients with tuberculosis. The influence of the genotypes on the pharmacokinetics of isoniazid was also evaluated. A total of 33 participants participated in the study and received isoniazid 300 mg once daily. Evaluable participants consist of ten slow (SA), fourteen intermediate (IA) and six rapid acetylators (RA). As expected, isoniazid exposure was higher (mean AUC, 28.4 versus 7.6 mg*h/L) and systemic clearance lower (mean apparent clearance, 14.8 versus 50.6 L/h) in SAs than RAs. The formulas to estimate isoniazid exposure were constructed using one or more concentration-time points that correlate with the area under the concentration-time curve (AUC). The LSS using a formula of single concentration-time point at 4 h post dose (C₄) is applicable for all acetylators to the therapeutic drug monitoring (TDM) of isoniazid in patients with tuberculosis when evaluated using the Deming regression and Bland-Altman plot (AUC = 1.53 + 10.03*C₄, adjusted r² = 0.95, p < 0.001). Considering that SAs are more prone to adverse effects, pre-dose NAT2 genotyping would be valuable for optimal isoniazid dosing in conjunction with TDM.

考虑到韩国肺结核患者的N-乙酰转移酶 2 ( NAT2 ) 基因型，开发了一种有限采样策略 (LSS) 来估计异烟肼的暴露量。还评估了基因型对异烟肼药代动力学的影响。共有 33 名参与者参与了这项研究，并每天服用 300 毫克异烟肼。可评估的参与者包括 10 名慢速 (SA)、14 名中速 (IA) 和 6 名快速乙酰化 (RA)。正如预期的那样，异烟肼暴露较高（平均 AUC，28.4与7.6 mg*h/L），全身清除率较低（平均表观清除率，14.8与50.6 L/h) 在 SAs 中比在 RAs 中。使用与浓度-时间曲线下面积 (AUC) 相关的一个或多个浓度-时间点构建估计异烟肼暴露量的公式。当使用 Deming 回归和 Bland-Altman 图进行评估时，使用剂量后 4 小时 (C ₄ )单浓度-时间点公式的 LSS适用于所有乙酰化剂对结核病患者的异烟肼治疗药物监测 (TDM) （AUC = 1.53 + 10.03*C ₄，调整后的 r ²  = 0.95，p < 0.001）。考虑到 SA 更容易产生不良反应，给药前NAT2基因分型对于结合 TDM 的最佳异烟肼给药是有价值的。