基于机制的群体药代动力学分析评估在孕妇中将依非韦伦剂量减少至 400mg 的可行性。
A Mechanism-Based Population Pharmacokinetic Analysis Assessing the Feasibility of Efavirenz Dose Reduction to 400 mg in Pregnant Women.
机构信息
Department of Pharmacy, Radboud Institute for Health Sciences (RIHS), Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands.
出版信息
Clin Pharmacokinet. 2018 Nov;57(11):1421-1433. doi: 10.1007/s40262-018-0642-9.
BACKGROUND
Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dose is adequate during pregnancy.
METHODS
We developed a mechanistic population pharmacokinetic model using pooled data from women included in seven studies (1968 samples, 774 collected during pregnancy). Total and free efavirenz exposure (AUC and C) were predicted for 400 (reduced) and 600 mg (standard) doses in both pregnant and non-pregnant women.
RESULTS
Using a 400 mg dose, the median efavirenz total AUC and C during the third trimester of pregnancy were 91 and 87% of values among non-pregnant women, respectively. Furthermore, the median free efavirenz C and AUC were predicted to increase during pregnancy by 11 and 15%, respectively.
CONCLUSIONS
It was predicted that reduced-dose efavirenz provides adequate exposure during pregnancy. These findings warrant prospective confirmation.
背景
降低依非韦伦的剂量可以提高安全性、降低成本，并增加 HIV 感染患者的治疗机会。根据世界卫生组织的建议，对于普遍推广，所有患者群体都应采用类似的剂量策略；然而，在怀孕期间，每日 400 毫克的剂量是否足够仍然未知。
方法
我们使用来自七个研究（1968 个样本，774 个在怀孕期间采集）中纳入的女性的数据，开发了一种基于机制的群体药代动力学模型。对于 400 毫克（减少剂量）和 600 毫克（标准剂量），我们预测了在怀孕和非怀孕女性中的总依非韦伦暴露量（AUC 和 C）和游离依非韦伦暴露量（C 和 AUC）。
结果
使用 400 毫克剂量时，妊娠晚期依非韦伦总 AUC 和 C 的中位数分别为非怀孕女性的 91%和 87%。此外，预测在怀孕期间游离依非韦伦 C 和 AUC 中位数将分别增加 11%和 15%。
结论
预测减少剂量的依非韦伦在怀孕期间可以提供足够的暴露量。这些发现需要前瞻性证实。
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