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已发表论文
注射用丙泊酚钠在肝功能损害受试者与健康匹配对照者中的药代动力学及安全性：一项前瞻性队列研究
Authors Wang R, Jiang X, Cao Q, Zhang W
Received 9 June 2025
Accepted for publication 8 October 2025
Published 17 October 2025 Volume 2025:19 Pages 9355—9366
DOI https://doi.org/10.2147/DDDT.S545798
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Tin Wui Wong
Rong Wang,1,2,* Xiaojuan Jiang,1,* Qiongfang Cao,1 Weiyi Zhang1
1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Anesthesiology, Mianyang 404 Hospital, Mianyang, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Weiyi Zhang, Email zhangweiyi@wchscu.cn
Purpose: Fospropofol disodium for injection (FospropofolFP) is a new water-soluble propofol prodrug for procedural sedation and general anesthesia. This prospective cohort study aimed to characterize the pharmacokinetics and safety of FospropofolFP in subjects with hepatic impairment compared with healthy matched participants during general anesthesia.
Patients and Methods: Twenty-three patients were enrolled and divided into three cohorts according to liver function: normal liver function (n = 10), moderate hepatic impairment (n = 10), and severe hepatic impairment (n = 3). They received a single bolus of FospropofolFP 10 mg/kg i.v. Venous blood samples were collected from each patient 14 time points. The plasma concentrations of FospropofolFP and active metabolite propofol were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by non-compantmental analysis (NCA) using Phoenix WinNonlin software.
Results: Compared with matched healthy controls, patients with moderate hepatic impairment exhibited significant reduced exposure and increased elimination for FospropofolFP: the area under the curve (AUC) decreased by approximately 43% and clearance (CL) increased by 60%. The AUC of patients with severe hepatic impairment exhibited a significant decrease by approximately 55%. Notably, propofol (active metabolite) clearance decreased by approximately 15% and 33% in moderate and severe impairment, respectively. Multivariate analysis identified preoperative albumin (ALB) as an independent predictor of FospropofolFP exposure.
Conclusion: Our study is the first to report altered PK of FospropofolFP in patients with moderate-to-severe hepatic impairment, report a reverse pattern of increased elimination of FospropofolFP and slow elimination of the metabolite propofol, and identify ALB as an independent predictor of FospropofolFP’s PK. No unexpected adverse events related to FospropofolFP were seen in subjects with hepatic impairment after a single dose and that repeated dosing may need further evaluation.
Keywords: hepatic impairment, fospropofol disodium, pharmacokinetic, propofol, safety
1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Anesthesiology, Mianyang 404 Hospital, Mianyang, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Weiyi Zhang, Email zhangweiyi@wchscu.cn
Purpose: Fospropofol disodium for injection (FospropofolFP) is a new water-soluble propofol prodrug for procedural sedation and general anesthesia. This prospective cohort study aimed to characterize the pharmacokinetics and safety of FospropofolFP in subjects with hepatic impairment compared with healthy matched participants during general anesthesia.
Patients and Methods: Twenty-three patients were enrolled and divided into three cohorts according to liver function: normal liver function (n = 10), moderate hepatic impairment (n = 10), and severe hepatic impairment (n = 3). They received a single bolus of FospropofolFP 10 mg/kg i.v. Venous blood samples were collected from each patient 14 time points. The plasma concentrations of FospropofolFP and active metabolite propofol were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by non-compantmental analysis (NCA) using Phoenix WinNonlin software.
Results: Compared with matched healthy controls, patients with moderate hepatic impairment exhibited significant reduced exposure and increased elimination for FospropofolFP: the area under the curve (AUC) decreased by approximately 43% and clearance (CL) increased by 60%. The AUC of patients with severe hepatic impairment exhibited a significant decrease by approximately 55%. Notably, propofol (active metabolite) clearance decreased by approximately 15% and 33% in moderate and severe impairment, respectively. Multivariate analysis identified preoperative albumin (ALB) as an independent predictor of FospropofolFP exposure.
Conclusion: Our study is the first to report altered PK of FospropofolFP in patients with moderate-to-severe hepatic impairment, report a reverse pattern of increased elimination of FospropofolFP and slow elimination of the metabolite propofol, and identify ALB as an independent predictor of FospropofolFP’s PK. No unexpected adverse events related to FospropofolFP were seen in subjects with hepatic impairment after a single dose and that repeated dosing may need further evaluation.
Keywords: hepatic impairment, fospropofol disodium, pharmacokinetic, propofol, safety