title: Propofol target-controlled infusion modeling in rabbits: Pharmacokinetic and pharmacodynamic analysis.
abstract: 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 WinNonlin 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/mL, while 12.52±0.69 μg/mL 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/mL (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.
authors.affiliation: Department of Anesthesiology, Shenzhen Baoan Hospital Affiliated to Southern Medical University, Shenzhen, 518100, China.
authors.forename: Jian-Yan
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Shang-Long
authors.initials: SL
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, Shenzhen People's Hospital, Shenzhen, 518020, China. zhxuep@sina.com.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Zhang
mesh_terms: D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D016903:Drug Monitoring; D007262:Infusions, Intravenous; D015233:Models, Statistical; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D012984:Software
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol
keywords: anesthetic depth; modeling; pharmacodynamics; pharmacokinetics; propofol; rabbit; target-controlled infusion