The purpose of this study was to observe and compare the differences in plasma concentration, dosage and carboxylesterase 1 activity of remimazolam when remimazolam is used for general anesthesia induction and maintenance at different times of the day, and to explore the effect of time rhythm on the pharmacokinetics and pharmacodynamics of remimazolam, so as to provide new ideas and clinical basis for optimizing medication regimens and anesthesia management.

This study is a single-blind, prospective cohort study. It is mainly divided into two parts: 1. Detection of the blood concentration and dosage differences of remimazolam: Patients who were scheduled to undergo laparoscopic cholecystectomy under general anesthesia were included. The patients were divided into the morning group (operation time 8:00-12:00) and the afternoon group (operation time 14:00-18:00) according to the operation time. The blood concentration of remimazolam after anesthesia induction was measured, and the influence of time rhythm on the pharmacokinetics of remimazolam was statistically analyzed. The dosage of remimazolam used during anesthesia maintenance was measured, and statistical analysis was conducted on whether there were dosage differences and the temporal rhythm of drug efficacy of remimazolam during the maintenance process. 2. CES1 Activity detection: Patients who were scheduled to undergo laparoscopic partial hepatectomy under general anesthesia were included. The research subjects were divided into the morning group (8:00-12:00) and the afternoon group (14:00-18:00) based on the liver tissue sampling time. The activity of carboxylate esterase 1 (CES1) in the normal tissues adjacent to liver cancer in patients at different time points was measured. Analyze the influence of time rhythm on the drug metabolism of remimazolam. The effects of time rhythm on the pharmacokinetics and pharmacodynamics of remimazolam were jointly verified from three aspects: blood drug concentration, drug dosage, and CES1 activity.

Inclusion Criteria:

Experiment 1: Measurement Experiment of Remimazolam Blood Concentration and Dosage

1. Age 18-65 years old, ASAI-II class, BMI18.5-25kg/m^2;
2. Inpatients undergoing laparoscopic cholecystectomy;
3. The estimated time of operation is 1.5~2.5 hours;
4. Voluntary participation and signed informed consent.

Experiment 2: Remimazolam metabolic enzyme CES1 activity measurement experiment

1. Age 18-75 years old, ASAI-III class;
2. Inpatients undergoing laparoscopic partial hepatic resection;
3. Voluntary participation and signed informed consent.

Exclusion Criteria:

Experiment 1:Measurement Experiment of Remimazolam Blood Concentration and Dosage

1. Pregnant or lactating women;
2. Patients who are allergic to remazolam or contraindicated;
3. Patients who are dependent on or tolerant to opioids or have long-term alcoholism;
4. Serious cardiovascular system, respiratory system, liver and kidney diseases;
5. History of obstructive sleep apnea;
6. Mental disorders or neurological diseases;
7. Patients who participated in clinical trials of other drugs within the last 3 months;
8. The attending physician or researcher considers that there are other circumstances that are not suitable for participation in this study;
9. Refuse to participate in the study

Experiment 2: Remimazolam metabolic enzyme CES1 activity measurement experiment

1. Pregnant or lactating women;
2. Patients who are allergic to remazolam or contraindicated;
3. Patients who are dependent on or tolerant to opioids or have long-term alcoholism;
4. Serious cardiovascular system, respiratory system;
5. History of obstructive sleep apnea;
6. Mental disorders or neurological diseases;
7. Patients who participated in clinical trials of other drugs within the last 3 months;
8. The attending physician or researcher considers that there are other circumstances that are not suitable for participation in this study;
9. Refuse to participate in the study

Experiment 1: Measurement Experiment of Remimazolam Blood Concentration and Dosage

1. Age 18-65 years old, ASAI-II class, BMI18.5-25kg/m^2;
2. Inpatients undergoing laparoscopic cholecystectomy;
3. The estimated time of operation is 1.5~2.5 hours;
4. Voluntary participation and signed informed consent.

Experiment 2: Remimazolam metabolic enzyme CES1 activity measurement experiment

1. Age 18-75 years old, ASAI-III class;
2. Inpatients undergoing laparoscopic partial hepatic resection;
3. Voluntary participation and signed informed consent.