Clinical trial NCT03422315: Population Pharmacokinetics and Clinical Individual Dosage Regimen of Propofoll Injection
Official title: Population Pharmacokinetics and Clinical Individual Dosage Regimen of Propofoll Injection in Adult Patients With General Anesthesia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: General Anesthesia
Keywords: Propofol
Population pharmacokinetics
Individualized administration
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.).

Primary outcomes:
measure: BIS
timeFrame: 210min
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital，Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: zhongyuan xu, Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.