Population Pharmacokinetics and Clinical Individual Dosage Regimen of Propofoll Injection

Population Pharmacokinetics and Clinical Individual Dosage Regimen of Propofoll Injection in Adult Patients With General Anesthesia

Propofol is a widely used sedative anesthetic, but there are large individual differences, which making different patients with different sensitivity to propofol. The aim of this study was to analyze the effects of age, height, body weight, Drinking, metabolic enzymes CYP2B6 and UGT1A9 on Pharmacological effects and pharmacokinetics of propofol, and to provide a reasonable reference for clinical anesthesia patients and evidence for individual dosage regimens.

Study Overview

• Status: Recruiting
• Conditions: General Anesthesia
• Intervention / Treatment: Drug: Propofol

Detailed Description

Propofol is a widely used sedative anesthetic, but there are large individual differences, which making different patients with different sensitivity to propofol. In recent years, the concept of individualized administration came into being.Individual administration refers to according to the condition of patients,the drug's safety and efficacy, and pharmacokinetics, pharmacodynamics and clinical response ,then gives different dosing regimens for individual patients and promotes the development of rational drug use. Different people have differences metabolism of propofol, reported in the literature, genetic polymorphism, demographic characteristics, combined with drug and other variability factors, all of them will affect the pharmacokinetics and pharmacodynamics of propofol.The aim of this study was to analyze the effects of age, height, body weight, Drinking, metabolic enzymes CYP2B6 and UGT1A9 on Pharmacological effects and pharmacokinetics of propofol, and to provide a reasonable reference for clinical anesthesia patients and evidence for individual dosage regimens.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: zhongyuan xu, Ph.D.; Phone Number: 020-62787926 13926186470; Email: nfyygcp@126.com
• Study Contact Backup: Name: wanwen cao, master; Phone Number: 020-62787926 13631304126; Email: nfyygcp@126.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital，Southern Medical University
      • Contact: zhongyuan xu, Ph.D; Email: nfgcp@126.com
      • Contact: wanwen cao, master; Email: nfyyqc@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients aged 18-60 years (including those aged 18 and 60) who underwent gastrointestinal endoscopy;
• weight should not be less than (≥) 50kg, not more than (≤) 80kg. Body mass index (BMI) = body weight kg / [(height m) 2], in the normal range of 19 to 25;
• American Society of Anesthesiologists (ASA) grading (Appendix I): I or II;
• no heart, liver, lung, kidney, digestive tract, nervous system, mental disorders and other medical history, no blood and metabolic diseases and other medical history, no potential difficulties airway and special past history,
• blood, urine, stool routine, liver and kidney function, blood lipids, ECG, chest X-ray and blood pressure normal, or abnormal but no clinical significance, the researchers believe that can be grouped.
• agree and sign informed consent.

Exclusion Criteria:

• important organs have primary disease;
• persons with mental or physical disabilities;
• those suffering from neurological or mental illness, a history of epilepsy;
• patients with cardiovascular or respiratory insufficiency and hypovolemia;
• obese or those with dyslipidemia;
• hereditary acute porphyria;
• infections, especially those with respiratory and central infections;
• language exchange barriers;
• suspected or indeed a history of alcohol, drug abuse; especially long-term use of non-steroidal anti-inflammatory drugs, opioids, tranquilizers;
• allergies, if the history of drugs or food allergies; or known to propofol, soybeans, peanuts, coconut oil allergy;
• smoking history (smoking ≥ 5 per day);
• 2 weeks before the trial had used all kinds of Chinese and Western medicine;
• the last 3 months of blood donors and test blood donors;
• other circumstances that the researcher thinks can not be grouped (eg, frail, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: External control; propofol;injection;2mg/kg;single-dose	Drug: Propofol; injection;2mg/kg;single-dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BIS	bispectral index monitoring	210min

Collaborators and Investigators

• Sponsor: Zhongyuan Xu
• Investigators: Study Director: zhongyuan xu, Ph.D., Nanfang Hospital of Southern Medical University

Publications and helpful links

General Publications

• Kansaku F, Kumai T, Sasaki K, Yokozuka M, Shimizu M, Tateda T, Murayama N, Kobayashi S, Yamazaki H. Individual differences in pharmacokinetics and pharmacodynamics of anesthetic agent propofol with regard to CYP2B6 and UGT1A9 genotype and patient age. Drug Metab Pharmacokinet. 2011;26(5):532-7. doi: 10.2133/dmpk.dmpk-11-rg-039. Epub 2011 Aug 23.
• Bernard O, Guillemette C. The main role of UGT1A9 in the hepatic metabolism of mycophenolic acid and the effects of naturally occurring variants. Drug Metab Dispos. 2004 Aug;32(8):775-8. doi: 10.1124/dmd.32.8.775.
• Takahashi H, Maruo Y, Mori A, Iwai M, Sato H, Takeuchi Y. Effect of D256N and Y483D on propofol glucuronidation by human uridine 5'-diphosphate glucuronosyltransferase (UGT1A9). Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):131-6. doi: 10.1111/j.1742-7843.2008.00247.x.
• Khan MS, Zetterlund EL, Green H, Oscarsson A, Zackrisson AL, Svanborg E, Lindholm ML, Persson H, Eintrei C. Pharmacogenetics, plasma concentrations, clinical signs and EEG during propofol treatment. Basic Clin Pharmacol Toxicol. 2014 Dec;115(6):565-70. doi: 10.1111/bcpt.12277. Epub 2014 Jul 19.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2018
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Propofol; Population pharmacokinetics; Individualized administration
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: C1033453

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: No
• Studies a U.S. FDA-regulated device product: No