Population pharmacokinetic-pharmacodynamic analysis and dose optimisation of ciprofol in paediatric anaesthesia.

BACKGROUND

We aimed to explore the population pharmacokinetics and pharmacodynamics (popPK/PD) of ciprofol in paediatric patients and to provide references for dose optimisation of ciprofol as initiation and maintenance dosages in paediatric patients.

METHODS

Anaesthesia was induced with ciprofol at doses of 0.6 mg kg-1 or 0.9 mg kg-1 in paediatric patients (n=88; 0.08-15 yr; weight, 4.2-71.0 kg) undergoing cardiac or thoracic surgery. Blood samples were collected using opportunistic blood sampling, and ciprofol concentration was determined by a validated analytical method. A popPK/PD model of ciprofol was developed. The relationship between bispectral index (BIS) and drug concentration was characterised by an effect compartment model in children younger than 3 yr of age.

RESULTS

A two-compartment model with body weight and an empirical maturation process as covariates optimally characterised ciprofol PK. The recommended induction dose was 0.6 mg kg-1. Maintenance of anaesthesia which targeted an optimal BIS range of 40-60 using simulation-based, weight-stratified infusion regimens was recommended as follows: 1.4 mg kg-1 h-1 for patients weighing 0-5 kg, 1.2 mg kg-1 h-1 for those weighing 5-30 kg, and 1.0 mg kg-1 h-1 for patients weighing >30 kg, with escalation to higher doses only under continuous BIS monitoring to avoid oversedation.

CONCLUSIONS

A ciprofol induction dose of 0.6 mg kg-1 followed by a weight-stratified maintenance infusion of 1.0-1.4 mg kg-1 h-1 is recommended for paediatric anaesthesia. Extrapolation to children 3 yr of age and older assumed similarity in PD response, and potential inaccuracy in this age group is cautioned.

CLINICAL TRIAL REGISTRATION: ChiCTR2600118090.