Population Pharmacokinetics and Pharmacodynamics of Ciprofol

Population Pharmacokinetic/Pharmacodynamic Modeling of Ciprofol in Elderly Patients Undergoing Orthopedic Limb Surgery

The goal of this observational study is to learn how the anesthetic drug ciprofol works in older adults who are having limb surgery under general anesthesia at Shanghai Geriatric Medical Center. The study will help researchers build a population model to better understand how the drug moves through the body (PK) and how it affects patients (PD). This model may help doctors use a Target-Controlled Infusion (TCI) system to adjust the drug dose more precisely.

The main question it aims to answer is: Does ciprofol work safely and effectively in older adults during orthopedic surgery?

Participants already receiving ciprofol as part of their regular anesthesia care will:

1. Provide blood samples at different time points during and after surgery.
2. Have their vital signs and anesthesia-related data recorded before, during, and after surgery.
3. Be monitored for side effects and recovery indicators such as the Aldrete score and signs of postoperative delirium.

Researchers will use this information to:

1. Build and test a population PK/PD model for ciprofol.
2. Simulate recommended TCI dosing plans.
3. Explore how individual responses to ciprofol relate to recovery and safety outcomes.

This study may help improve anesthesia care for elder adults by making drug dosing safer and more effective.

Study Overview

• Status: Recruiting
• Conditions: Femoral Neck Fractures; Hip Fractures (ICD-10 72.01-72.2); Osteoarthritis, Knee and Hip
• Intervention / Treatment: Drug: Ciprofol

Detailed Description

Elderly patients undergoing orthopedic limb surgery represent a growing population with unique perioperative challenges. Age-related physiological changes-including reduced hepatic and renal function, altered body composition, and decreased cardiac output-significantly affect the pharmacokinetics (PK) and pharmacodynamics (PD) of anesthetic drugs. These changes increase the difficulty of maintaining adequate anesthesia depth and hemodynamic stability.

Ciprofol, a novel intravenous anesthetic, has shown promising efficacy and safety in clinical practice. However, existing PK/PD models are largely derived from healthy volunteers or younger patients, and cannot adequately predict drug behavior in elderly orthopedic patients who often present with comorbidities and heightened surgical stress. This gap may lead to risks such as drug accumulation and circulatory depression, or insufficient dosing and intraoperative awareness.

This single-center, observational, prospective study at Shanghai Geriatric Medical Center aims to construct and validate a population PK/PD model of ciprofol specifically for elderly patients undergoing orthopedic limb surgery. The model will support precise control of effect-site concentration via Target-Controlled Infusion (TCI) systems, enabling individualized anesthesia management.

Study Objectives 1.Primary Objective: To develop and validate a population PK/PD model of ciprofol tailored to elderly orthopedic patients, and to evaluate its accuracy in predicting effect-site concentrations.

2.Secondary Objectives:

1. To simulate recommended TCI dosing regimens based on the new model and compare them with current drug label recommendations, assessing clinical value and optimization potential.
2. To evaluate the anesthetic efficacy and safety of ciprofol in this patient population.

3.Exploratory Objectives: To investigate the influence of covariates (e.g., age, sex, BMI, hepatic and renal function) on PK/PD parameters, and to explore correlations between individual PK/PD parameters and recovery outcomes such as Aldrete score and postoperative delirium incidence.

Study Design

1.Type: Single-center, observational, biosample-utilization study. 2.Population: 45 elderly patients (≥65 years, ASA I-III) scheduled for elective orthopedic limb surgery under general anesthesia.

3.Procedures:

1. Collection of perioperative clinical data (vital signs, BIS monitoring, anesthesia-related indicators).
2. Serial blood sampling at predefined time points for plasma concentration measurement.
3. Monitoring of anesthetic efficacy (induction success, BIS values, recovery times) and safety endpoints (hypotension, bradycardia, hypoxemia, injection pain).

4.Endpoints:

1. Primary Endpoint: Accuracy of the population PK/PD model in predicting effect-site concentrations.
2. Secondary Endpoints: Differences between model-recommended dosing and label-based dosing; incidence of ciprofol-related adverse events; anesthetic efficacy indicators.
3. Exploratory Endpoints: Covariate effects on PK/PD parameters; correlation of PK/PD parameters with Aldrete score recovery and postoperative delirium.

Data Management and Analysis All perioperative data will be recorded and stored electronically, with double-entry verification and query resolution procedures to ensure accuracy. PK/PD modeling will be performed using nonlinear mixed-effects modeling (NONMEM). Model evaluation will include goodness-of-fit plots, visual predictive checks, and bootstrap validation. Simulations will be conducted to compare TCI dosing regimens derived from the new model with standard recommendations.

Expected Significance This study will fill an important gap in anesthetic pharmacology by providing a validated PK/PD model of ciprofol for elderly orthopedic patients. The findings are expected to improve perioperative anesthesia management, enhance patient safety, and support individualized dosing strategies in clinical practice.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Xue Zhang; Phone Number: 02164175590; Email: zx02190554@126.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Geriatric Medical Center
    • Contact: Clinical Research Coordinator; Phone Number: 021-64175590; Email: zx02190554@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Elderly patients undergoing orthopedic limb surgery

Description

Inclusion Criteria:

• Age ≥65 years;
• BMI: 18-30 kg/m²;
• ASA physical status classification I-III;
• Scheduled for elective orthopedic limb surgery under general anesthesia;
• Expected duration of surgery >30 minutes;
• Willing to participate and able to provide written informed consent.

Exclusion Criteria:

• Known allergy to ciprofol or related medications, or any contraindication to their use;
• Preoperative cognitive impairment;
• History of severe cerebrovascular disease or related complications;
• History of neuromuscular system diseases or psychiatric disorders;
• History of sedative medication use;
• History of alcohol abuse or substance use disorder;
• Bradycardia (heart rate <60 beats per minute);
• Hypotension (mean arterial pressure <55 mmHg);
• QT interval prolongation;
• Uncooperative or unable to communicate effectively.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Elderly Orthopedic Limb Surgery Cohort; Inclusion Criteria: Age ≥65 years; BMI 18-30 kg/m²; ASA physical status classification I-III; Scheduled for elective orthopedic limb surgery under general anesthesia; Expected duration of surgery >30 minutes; Willing to participate and able to provide written informed consent. Exclusion Criteria: Known allergy to ciprofol or related medications, or any contraindication to their use; Preoperative cognitive impairment (Mini-Cog score <3); History of severe cerebrovascular disease or related complications; History of neuromuscular system diseases or psychiatric disorders; History of sedative medication use; History of alcohol abuse or substance use disorder; Bradycardia (heart rate <60 beats per minute); Hypotension (mean arterial pressure <55 mmHg); QT interval prolongation; Uncooperative or unable to communicate effectively.

Drug: Ciprofol; Ciprofol is used as an intravenous anesthetic agent for sedation and anesthesia induction/maintenance in elderly patients undergoing elective orthopedic limb surgery. In this observational study, ciprofol is administered according to standard clinical practices, and data on its pharmacokinetics, pharmacodynamics, safety, and effectiveness in this specific population will be collected.; Other Names: Cipepofol; Sishuning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Ciprofol	Arterial or venous blood samples (1 mL each) will be collected to measure the plasma concentration of ciprofol using liquid chromatography - mass spectrometry. These concentration data points will be used to construct the population pharmacokinetic model. Reported in ng/mL.	From the start of drug administration to 24 hours after the end of drug administration.
Bispectral Index (BIS) Value	The BIS value is a non-invasive measure of the level of consciousness/depth of anesthesia, ranging from 0 (isoelectric EEG) to 100 (awake). It is used as the pharmacodynamic metric for modeling.	Continuously monitored from the start of anesthesia induction, throughout the maintenance phase, until full recovery (approximately up to 4 hours).
Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score	The MOAA/S scale is a categorical measure used to assess the depth of sedation/anesthesia. Scores range from 0 (No response to painful stimulus) to 5 (Responds readily to name spoken in normal tone). This metric will be used as a pharmacodynamic endpoint to construct a categorical PK/PD model (e.g., proportional odds model) relating ciprofol concentration to clinical sedation depth.	Induction phase (every minute until loss of consciousness); Maintenance phase; and Post-operative phase (every 3 minutes in PACU until score returns to 5), up to approximately 4 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Arterial Pressure (MAP)	Evaluation of hemodynamic stability by measuring the absolute value of Mean Arterial Pressure. Reported in millimeters of mercury (mmHg).	Continuously measured during the induction, maintenance (intra-operative), and recovery phase (up to 2 hours post-infusion).
Heart Rate	Evaluation of hemodynamic stability by measuring the absolute value of Heart Rate. Reported in beats per minute (bpm).	Continuously measured during the induction, maintenance (intra-operative), and recovery phase (up to 2 hours post-infusion).

Collaborators and Investigators

• Sponsor: Shanghai Geriatric Medical Center
• Investigators: Principal Investigator: Xue Zhang, Shanghai Geriatric Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 10, 2025
• First Posted (Actual): December 24, 2025

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Wounds and Injuries; Arthritis; Joint Diseases; Rheumatic Diseases; Leg Injuries; Fractures, Bone; Femoral Fractures; Hip Injuries; Osteoarthritis; Hip Fractures; Femoral Neck Fractures; (2-(1R)-1-cyclopropyl)ethyl-6-isopropyl-phenol
• Other Study ID Numbers: ZCLY2025-021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No