Clinical trial NCT02070614: Association of CYP3A4 rs2242480 With Sufentanil Plasma Concentration and PCA Consumption
Official title: Association of CYP3A4 rs2242480 With Sufentanil Plasma Concentration and PCA Consumption
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Surgery
Individuality
Keywords: sufentanil
metabolism
cytochrome P450 3A4
gene polymorphism
Lead sponsor: Huazhong University of Science and Technology
Sponsor class: OTHER
First posted: 2014-02-25
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Sampling method: PROBABILITY_SAMPLE
Study population: 60 Chinese male and female patients receiving elective upper abdominal surgery (liver, pancreatic, gallbladder) under general anesthesia

Brief summary: This study was designed for exploring the association of cytochrome P450 3A4 rs2242480 polymorphism with metabolism of sufentanil in Chinese patients receiving upper abdominal surgery，to provide evidence for genetic prediction of personalized medication.Methods:60 patients who prepared for elective upper abdominal surgery under general anesthesia were recruited into study. Liver enzyme inhibitor should be excluded in anesthesia. rs2242480 genotyping was carried out by direct sequencing. The blood samples were drawn before anesthesia，30 min and 45min after anesthesia respectively，used for plasma sufentanil concentration detection with high performance liquid chromatography-mass spectrometry (HPLC-MS). After surgery，the patients received patient-controlled intravenous sufentanil immediately. And postoperative pain at rest，sufentanil consumption，side effects and rescue analgesic requirements were recorded at the 6th，12th，24th hour. The plasma sufentanil concentration and PCA sufentanil consumption were analyzed to investigate the differences among rs2242480 three genotypes.

Detailed description: The study consisted of healthy men and women between 18 to 65 years of age.

Participants were screened and stratified according to cytochrome P450 3A4 rs2242480 genotype:

* 1/\*1 Grouped by rs2242480 polymorphism, wild-type homozygote
* 1/\*1G Grouped by rs2242480 polymorphism,\*1/\*1G: mutant heterozygote
* 1G/\*1G Grouped by rs2242480 polymorphism,\*1G/\*1G: mutant homozygote

Eligibility criteria: Inclusion Criteria:

* 1.American Society of Anesthesiologists (ASA) physical status I or II 2.age from 18 to 65 years old 3.BMI of 19～26kg/m2

Exclusion Criteria:

* 1.known history of chronic pain, psychiatric diseases, diabetes mellitus, severe cardiovascular diseases, kidney or liver diseases with poor hepatic function 2.alcohol or drug abuse (according to the criteria of Diagnostic and Statistical Manual of Mental Disorders-IV) 3.pregnancy or at lactation period 4.Patients who consumed drugs (1 week) or foods (3 days) known to inhibit or induce the expression of cytochrome P450 3A4 enzymes prior to surgery were also excluded. The following drugs or foods included but were not limited to erythromycin, clarithromycin, alcohol, chocolate, coffee, grapefruit juice, verapamil, rifampicin, HIV protease inhibitors, phenytoin,itraconazole, dexamethasone, phenobarbital, and carbamazepine.

Primary outcomes:
measure: the correlation between rs2242480 polymorphism and sufentanil metabolism
timeFrame: 4 months
Secondary outcomes:
measure: Variation of plasma concentration of sufentanil
timeFrame: 4 months
measure: relation between rs2242480 genotype and patient-controlled analgesia(PCA) consumption of sufentanil
timeFrame: 4 months
measure: relation between Visual Analogue Scale/Score(VAS) and rs2242480
timeFrame: 4 months
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Huazhong University of Science and Technology
name: Xianwei Zhang, MD
role: STUDY_DIRECTOR
References: