A Comparative Study of Pharmacokinetics and Pharmacodynamics of Continuous Ciprofol Infusion Between Young and Elderly Patients.

OBJECTIVE

This study aimed to systematically compare the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of continuous ciprofol infusion between young and elderly patients under general anesthesia, clarify the impact of age, and provide evidence for precise clinical drug use.

METHODS

This non-randomised design study enrolled a total of 40 patients scheduled for elective surgery, who were divided into a young group (20-45 years, n=20) and an elderly group (65-85 years, n=20). All participants received ciprofol for anesthesia induction (0.4 mg/kg) and maintenance (0.8 mg/kg/h). Arterial blood samples were collected at 20 predefined time points for plasma concentration analysis using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). PK parameters were determined using non-compartmental analysis. PD endpoints, including bispectral index (BIS) and the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale, were monitored simultaneously.

RESULTS

PK analysis revealed that compared with the young group, the elderly group exhibited a significant reduction in total body clearance (CL) of ciprofol (0.60 ± 0.09 vs. 0.75 ± 0.08 L/h/kg, p < 0.001) and a prolonged elimination half-life (t1/2) (3.40 ± 0.92 vs. 2.68 ± 0.51 h, p = 0.003), resulting in significantly increased drug exposure (AUC0-t, p = 0.016; AUC0-∞, p = 0.018). PD analysis showed that the elderly group achieved a deeper sedation; however, equivalence analysis confirmed clinical equivalence between the two groups for key BIS parameters (BIS peak and BIS AUC0-t). The exploratory PK-PD analysis suggested that the effective sedative plasma concentration range of ciprofol potentially falls between 400-700 ng/mL. Regarding safety, the incidence of adverse events was higher in the elderly group than in the young group.

CONCLUSION

Ciprofol exhibits delayed clearance and increased hemodynamic sensitivity in elderly patients. To achieve safe and effective anesthesia, enhanced intraoperative monitoring and individualized management strategies should be implemented for elderly patients.