Pharmacokinetics, pharmacodynamics, and safety of ciprofol emulsion in Chinese subjects with normal or impaired renal function

Abstract

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 (Cmax) 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.

Exploring Ciprofol Alternatives: A Comprehensive Review of Intravenous Anesthesia Options

“…Phase II clinical trials have demonstrated the pharmacokinetic equivalence of ciprofol to propofol in the induction and maintenance of general anesthesia for elective surgical procedures [1]. Regulatory approval has been granted for ciprofol's use in inducing and maintaining general anesthesia and for providing sedation in intensive care settings [6]. Furthermore, a comprehensive drug-drug interaction study has explored the impact of sodium divalproex on ciprofol in terms of pharmacokinetics and pharmacodynamics [7].…”

“…Ciprofol, a novel alternative to propofol in clinical intravenous anesthesia, operates primarily by enhancing the ion channel's activity mediated by GABAA receptors [1,5,6]. It functions as a positive allosteric modulator and direct agonist of the GABAA receptor, exhibiting a higher receptor affinity for ciprofol than propofol.…”

“…Moreover, its therapeutic index surpasses that of propofol by 1.5 times, suggesting potential for simplified clinical use, particularly among elderly patients. Nevertheless, further investigations are imperative to establish its enduring safety and efficacy, particularly when juxtaposed with propofol across diverse clinical contexts, as well as to discern potential drug-drug interactions [1,[5][6][7]9].…”

“…Continually assessing its safety profile remains critical, especially among surgical patients and those undergoing procedural sedation [10]. Ongoing investigations are concentrating on potential drug interactions and the impact of special populations, such as the elderly, on ciprofol's pharmacokinetics and clinical effects [6]. Despite its potential as an alternative intravenous anesthetic, addressing the aforementioned challenges through continued research and clinical evaluation is essential to ensure the safe and effective utilization of ciprofol across various patient demographics and clinical environments.…”