Pharmacokinetics, Pharmacodynamics, and Safety of Ciprofol Injectable in Chinese Subjects with Normal or Impaired Renal Function

Abstract

Purpose The study was designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of ciprofol injection in healthy subjects and patients with mild and moderate renal impairment, to provide a reference for the dosage adjustment in these populations. Methods A total of 24 subjects were enrolled in this study. An initial loading dose of ciprofol was 0.4 mg/kg for 1 min, followed by maintenance infusion at a rate of 0.4 mg/kg/h for 30 min were administered to subjects. To evaluate the PK of ciprofol and its metabolite M4, plasma and urine samples were collected. PD was evaluated 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 area under the curve (AUC) and maximum concentration (Cmax) of ciprofol in plasma for patients with renal impairment were only slightly higher (0.9- to 1.2-fold) than those subjects in with normal renal function. For the metabolite M4, AUC values were 1.3- and 2.1-fold greater in patients with mild and moderate renal impairment, respectively, than healthy controls. However, increased exposure to M4 in participants with renal impairment may not be clinically significant, as this metabolite is pharmacologically inactive. There was no obvious effect of renal impairment on the PD parameters. The study found that ciprofol injection was well-tolerated, with all AEs reported being mild or moderate in severity. Conclusion No dosage adjustment of ciprofol is necessary for patients with mild-to-moderate renal impairment who receive the injection. Clinical trial registration: NCT04142970(October, 2019).