Background 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. Methods 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. Results 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. Conclusions 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. Trial registration This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2200058405) on April 8, 2022 (<a href="https://www.chictr.org.cn/">https://www.chictr.org.cn/</a>).

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

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2026年1月30日

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Sicong Wang,
Yan Li,
Zhiyan Hu,
Longzhi Du,
Ying Wang,
Xiaoya Jiang,
Lujin Li,
Wangning Shangguan

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Trial registration

This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2200058405) on April 8, 2022 (https://www.chictr.org.cn/).