PMID- 38074142
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231211
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Pharmacokinetics, pharmacodynamics, and safety of ciprofol emulsion in Chinese 
      subjects with normal or impaired renal function.
PG  - 1260599
LID - 10.3389/fphar.2023.1260599 [doi]
LID - 1260599
AB  - Background: Ciprofol, a novel sedative-hypnotic drug, has been approved for its 
      use in inducing and maintaining general anesthesia, as well as for providing 
      sedation. Methods: In this phase I, single-center, parallel, controlled, 
      open-label clinical trial, our objective was to analyze the pharmacokinetics 
      (PK), pharmacodynamics (PD), and safety of ciprofol emulsion in 24 participants 
      with mild and moderate renal impairment (n = 8 per group) and matched healthy 
      participants (n = 8). An initial loading infusion of ciprofol was administered at 
      0.4 mg/kg for 1 min, followed by a maintenance infusion at a rate of 0.4 mg/kg/h 
      for 30 min. We collected plasma and urine samples from the participants to assess 
      the PK of ciprofol and its metabolite M4. The evaluation of PD involved using a 
      modified observer's alertness/sedation scale (MOAA/S) in combination with 
      bispectral index (BIS) monitoring. Safety assessments were conducted throughout 
      the trial process. Results: The plasma concentration-time curve of ciprofol in 
      participants with renal impairment was similar to that in participants with 
      normal kidney function. The area under the curve (AUC) and maximum concentration 
      (C(max)) of total and unbound ciprofol in plasma for participants with renal 
      impairment were only slightly higher (0.7-1.2-fold) than those in participants 
      with normal renal function. In contrast, for the metabolite M4, AUC values were 
      1.3- and 2.1-fold greater in participants with mild and moderate renal 
      impairment, respectively, than in healthy controls. However, renal impairment had 
      no significant impact on the PD parameters. The study found that ciprofol was 
      well-tolerated, with all adverse events (AEs) reported being mild or moderate in 
      severity. Conclusion: Based on these findings, we can conclude that no dosage 
      adjustment of ciprofol is necessary for patients with mild-moderate renal 
      impairment who receive the injection. Clinical Trial Registration: 
      https://clinicaltrials.gov, identifier NCT04142970.
CI  - Copyright (c) 2023 Tao, Liu, Zhao, Qi, Yan, Wu, Liu, Liu and Tian.
FAU - Tao, Jun
AU  - Tao J
AD  - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
AD  - Henan Provincial Key Laboratory of Precision Clinical Pharmacy, Zhengzhou 
      University, Zhengzhou, China.
FAU - Liu, Shuaibing
AU  - Liu S
AD  - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
AD  - Henan Provincial Key Laboratory of Precision Clinical Pharmacy, Zhengzhou 
      University, Zhengzhou, China.
FAU - Zhao, Ying Ying
AU  - Zhao YY
AD  - Department of Anesthesiology, Pain and Perioperative Medicine, The First 
      Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
FAU - Qi, Lei
AU  - Qi L
AD  - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Yan, Pangke
AU  - Yan P
AD  - Sichuan Haisco Pharmaceutical Group Co., Ltd., Chengdu, China.
FAU - Wu, Nan
AU  - Wu N
AD  - Sichuan Haisco Pharmaceutical Group Co., Ltd., Chengdu, China.
FAU - Liu, Xiao
AU  - Liu X
AD  - Sichuan Haisco Pharmaceutical Group Co., Ltd., Chengdu, China.
FAU - Liu, Dongwei
AU  - Liu D
AD  - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Tian, Xin
AU  - Tian X
AD  - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
AD  - Henan Provincial Key Laboratory of Precision Clinical Pharmacy, Zhengzhou 
      University, Zhengzhou, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT04142970
PT  - Journal Article
DEP - 20231123
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10704090
OTO - NOTNLM
OT  - anesthetic
OT  - ciprofol
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - renal impairment
OT  - safety
COIS- Authors PY, NW, and XiL were employed by Sichuan Haisco Pharmaceutical Group Co., 
      Ltd. The authors declare that this study received funding from Sichuan Haisco 
      Pharmaceutical Group Co., Ltd. The funder had the following involvement with the 
      study: study design, analysis and and the decision to submit it for publication.
EDAT- 2023/12/11 06:45
MHDA- 2023/12/11 06:46
PMCR- 2023/11/23
CRDT- 2023/12/11 05:39
PHST- 2023/07/18 00:00 [received]
PHST- 2023/11/03 00:00 [accepted]
PHST- 2023/12/11 06:46 [medline]
PHST- 2023/12/11 06:45 [pubmed]
PHST- 2023/12/11 05:39 [entrez]
PHST- 2023/11/23 00:00 [pmc-release]
AID - 1260599 [pii]
AID - 10.3389/fphar.2023.1260599 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Nov 23;14:1260599. doi: 10.3389/fphar.2023.1260599. 
      eCollection 2023.