Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Int J Antimicrob Agents. 2017 Mar;49(3):327-332. doi: 10.1016/j.ijantimicag.2016.11.019. Epub 2017 Jan 18.
There is evidence that Thai patients receiving standard doses of ritonavir (RTV)-boosted atazanavir (ATV/r) have high exposure to atazanavir (ATV) leading to a higher risk of toxicity. A lower dose of ATV/r may provide adequate exposure in this population. However, pharmacokinetic data on ATV/r in Thai patients required for dose adjustment are limited. This study aimed to develop a population pharmacokinetic model of ATV/r and to determine the influence of patient characteristics on ATV pharmacokinetics. Monte Carlo simulations were performed to estimate the proportion of patients achieving target ATV trough concentration (C) with the standard ATV/r dose of 300/100 mg and a low dose of 200/100 mg once daily (OD). A total of 127 Thai HIV-infected patients were included in this study. One random blood sample was collected to determine ATV and RTV concentrations at each clinic visit from 100 patients. Intensive data from 27 patients enrolled in previous studies were also included. Data were analysed using the non-linear mixed-effects modelling approach. A one-compartment model with first-order absorption and elimination and absorption lag time best described the data. The population mean clearance of ATV/r was 4.93 L/h in female patients and was 28.7% higher in male patients. Simulation results showed a higher proportion of patients achieving ATV C within the target range with ATV/r 200/100 mg compared with 300/100 mg. The 200/100 mg OD dose of ATV/r provides adequate ATV exposure in Thai HIV-infected patients. Therefore, a lower dose of ATV/r should be considered for Thai and Asian populations.
有证据表明，接受标准剂量利托那韦（RTV）增强的阿扎那韦（ATV/r）治疗的泰国患者对阿扎那韦（ATV）的暴露量较高，从而导致毒性风险增加。较低剂量的 ATV/r 可能在该人群中提供足够的暴露量。然而，用于剂量调整的泰国患者的 ATV/r 药代动力学数据有限。本研究旨在建立 ATV/r 的群体药代动力学模型，并确定患者特征对 ATV 药代动力学的影响。进行蒙特卡罗模拟，以估计在标准 ATV/r 剂量 300/100mg 和低剂量 200/100mg 每日一次（OD）时，达到目标 ATV 谷浓度（C）的患者比例。共有 127 名泰国 HIV 感染患者纳入本研究。从 100 名患者的每次就诊中随机采集一份血样以确定 ATV 和 RTV 浓度。还包括来自先前研究的 27 名患者的密集数据。使用非线性混合效应建模方法进行数据分析。一个一室模型，具有一级吸收和消除以及吸收滞后时间，可最佳描述数据。女性患者的 ATV/r 群体平均清除率为 4.93 L/h，男性患者的清除率高出 28.7%。模拟结果显示，与 ATV/r 300/100mg 相比，使用 ATV/r 200/100mg 时，达到 ATV C 目标范围的患者比例更高。在泰国 HIV 感染患者中，ATV/r 200/100mg OD 剂量可提供足够的 ATV 暴露量。因此，应该考虑为泰国和亚洲人群降低 ATV/r 的剂量。
