Propofol Target-Controlled Infusion Modeling in Rabbits： Pharmacokinetic and Pharmacodynamic Analysis

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 36; no. 3; pp. 428 - 433
• Main Author: 陈建颜 易明 姚尚龙 张雪萍
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.06.2016; Department of Anesthesiology, Shenzhen Baoan Hospital Affiliated to Southern Medical University, Shenzhen 518100, China%Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China%Department of Anesthesiology, Shenzhen People's Hospital Shenzhen 518020, China
• Subjects: Anesthetics, Intravenous - blood; Anesthetics, Intravenous - pharmacokinetics; Animals; Drug Monitoring; Infusions, Intravenous; Medicine; Medicine & Public Health; Models, Statistical; Propofol - blood; Propofol - pharmacokinetics; Rabbits; Software; 动力学模型; 动物体内; 大白兔; 学分; 异丙酚; 日本大耳白兔; 药代动力学; 药效学; modeling; target-controlled infusion; propofol; pharmacodynamics; rabbit; anesthetic depth; pharmacokinetics
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-016-1604-9

This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.