Population pharmacokinetics of a single bolus of ciprofol in Chinese pediatric patients

Ciprofol is a recently developed sedative similar to propofol, but there is a lack of bolus pharmacokinetic data for ciprofol in children. Improved knowledge of ciprofol pharmacokinetics (PK) in children could help in formulating dosing guidelines. We conducted a study involving pediatric surgical patients aged 1 to 9 years to analyze the population PK of ciprofol and to create a validated dosing plan for this group. We enrolled 27 children, aged between 1 and 9 years, with American Society of Anesthesiologists physical status score of I or II, who were scheduled for elective urologic surgery. A 0.6 mg/kg bolus of ciprofol was given over 30 s. Thirteen arterial blood samples were collected from each patient for analysis. Ultra-high performance liquid chromatography combined with mass spectrometry was used to measure the plasma concentrations of ciprofol. An analysis of population pharmacokinetics was executed using a nonlinear mixed-effects model, based on data collected through an intensive sampling design. Furthermore, safety evaluations were performed throughout the trial. Ciprofol PK were best described using a three-compartment model. The population estimates for the pharmacokinetic parameters were as follows: clearance (CL) was 31.2 ml/min/kg, the volume of distribution for the central compartment (V1) was 506 ml/kg, and the peripheral volumes of distribution were V2 = 231 ml/kg and V3 = 1360 ml/kg, the intercompartmental clearances were CL2 = 28.2 ml/min/kg and CL3 = 19.8 ml/min/kg. The statistical improvement of the model was achieved by using blood urea nitrogen (BUN) as the only covariate for V1, but its effect on ciprofol exposure was negligible and not of clinical significance. Furthermore, after administering the drug based on body weight, neither age nor body weight significantly influences the PK parameters of ciprofol. The study also found that ciprofol was well-tolerated, with no hemodynamic adverse events observed. Compared to adults, pediatric patients have higher CL and V1 per kilogram for ciprofol. This result aligns with the higher need for ciprofol in children aged 1 to 9 years. A 0.6 mg/kg induction dose of ciprofol is expected to provide similar exposure without causing drug-related side effects in children. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2200058405) on April 8, 2022 (https://www.chictr.org.cn/). • Ciprofol pharmacokinetics in children can be modeled as a three-compartment system following a single bolus induction dose. • The CL and V1 of ciprofol are larger than those reported in adults. • A 0.6 mg/kg induction dose of ciprofol is expected to provide similar exposure without causing adverse drug events in children.