NH600001 is a new general anaesthetic drug with a structure similar to etomidate. The objective of this study was to investigate the relationship between concentrations of NH600001 and sedation efficacy based on data from phase I-II studies and factors influencing the pharmacokinetics and pharmacodynamics of NH600001. The dataset consisted of 2 phase I studies in healthy subjects and 1 phase II study in patients undergoing gastroscopy. Nonlinear mixed effects modeling was used in developing the population pharmacokinetics and pharmacodynamics (PopPK/PD) model of NH600001. Three-compartment model was used to describe the PK profile of NH600001. Parameters were used for allometric scaling on body weight, where the exponents were set to 0.75 for clearance and 1 for volumes. Co-administration of alfentanil hydrochloride influenced the distribution volume of the central compartment and clearance. Effect of patients undergoing gastroscopy (compared with healthy subjects) on clearance, the distribution volume of the superficial peripheral compartment and inter-compartmental clearance for deep peripheral compartment and central compartment was included the final PopPK model. The effect compartment model well characterized the PK/PD relationship of NH600001. Simulation results showed that an initial dose of 0.25 mg/kg of NH600001 resulted in rapid sedation, and three additional doses at 5-min intervals could maintain sedation for more than 20 min. A PopPK/PD model was successfully constructed for NH600001 in healthy subjects and in patients undergoing gastroscopy that could inform the dosing regimens of the forthcoming phase III study.

Yaxin Liu

Yun Kuang

Jie Huang

Dan Jiang

Yajie Cao

Qi Gao

Zifeng Li

Wen Ouyang

Saiying Wang

Qi Pei

Guoping Yang

The AAPS Journal

AAPS 杂志是美国药物科学家协会 (AAPS) 的官方期刊，发表了影响人类和兽医治疗的药物科学各个领域的新颖而重要的发现，包括：· 药物设计和发现· 制药生物技术· 生物制药、制剂, 和药物递送· 代谢和运输· 药代动力学、药效学和药效学· 转化研究· 临床评估和治疗结果· 监管科学我们邀请以下文章类型提交：· 原创研究文章· 评论和小型评论· 白皮书、评论, 和社论· 会议报告· 简要/技术报告和快速通信· 监管说明· 教程· 药物科学协议此外，AAPS 期刊还发布由客座编辑组织的主题，重点关注我们领域当前感兴趣的特定领域.

AAPS Journal is the official journal of the American Association of Pharmaceutical Scientists (AAPS), publishing novel and significant findings across various fields of pharmaceutical science that impact human and veterinary therapeutics. The main topics include: drug design and discovery, pharmaceutical biotechnology, biopharmaceuticals, formulation and drug delivery, metabolism and transport, pharmacokinetics, pharmacodynamics, translational research, clinical evaluation and therapeutic outcomes, and regulatory science. We invite submissions of the following article types: original research articles, reviews and mini-reviews, white papers, commentaries and editorials, conference reports, brief/technical reports and rapid communications, regulatory guidelines, tutorials, and pharmaceutical science protocols. Additionally, AAPS Journal publishes themed issues organized by guest editors, focusing on specific areas of current interest in our field.

AAPS Journal 是美国药物科学家协会 (AAPS) 的官方期刊，发表影响人类和兽医治疗的药物科学各个领域的新颖而重要的发现。主要涵盖以下主题：药物设计与发现、制药生物技术、生物制药、制剂与药物递送、代谢与运输、药代动力学、药效学、转化研究、临床评估与治疗结果以及监管科学。我们欢迎以下类型的文章提交：原创研究文章、评论与小型评论、白皮书、评论与社论、会议报告、简要/技术报告与快速通信、监管说明、教程及药物科学协议。此外，AAPS Journal 还发布由客座编辑组织的主题，重点关注我们领域当前感兴趣的特定领域。

AAPS Journal

AAPS J

Pharmacokinetic-pharmacodynamic Modelling of NH600001 in Healthy Subjects and Patients Undergoing Gastroscopy

NH600001在健康受试者和接受胃镜检查患者中的药代动力学-药效学建模

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医学	3
医学, 药学	3

Pharmacokinetic-pharmacodynamic Modelling of NH600001 in Healthy Subjects and Patients Undergoing Gastroscopy

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PHARMACOLOGY & PHARMACY	1