Association of CYP3A4 rs2242480 With Sufentanil Plasma Concentration and PCA Consumption

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.

Study Overview

• Status: Completed
• Conditions: Surgery; Individuality

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

• Study Type: Observational
• Enrollment (Actual): 72

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

60 Chinese male and female patients receiving elective upper abdominal surgery (liver, pancreatic, gallbladder) under general anesthesia

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
rs2242480 wild-type homozygote; *1/*1 Grouped by rs2242480 polymorphism genotyping
rs2242480 mutant heterozygote; *1/*1G Grouped by rs2242480 polymorphism genotyping
rs2242480 mutant homozygote; *1G/*1G Grouped by rs2242480 polymorphism genotyping

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the correlation between rs2242480 polymorphism and sufentanil metabolism	according to rs2242480 genotype and plasma concentration of sufentanil	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of plasma concentration of sufentanil	the single-dose sufentanil plasma concentration varies between participants, and the differences among 3 time-points is related with personal genotype.	4 months
relation between rs2242480 genotype and patient-controlled analgesia(PCA) consumption of sufentanil	according to postoperative PCA sufentanil consumption and rs2242480 genotype	4 months
relation between Visual Analogue Scale/Score(VAS) and rs2242480	according to PCA VAS and rs2242480 genotype	4 months

Collaborators and Investigators

• Sponsor: Xianwei Zhang
• Investigators: Study Director: Xianwei Zhang, MD, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: February 23, 2014
• First Submitted That Met QC Criteria: February 23, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): September 1, 2015
• Last Update Submitted That Met QC Criteria: August 30, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: sufentanil; metabolism; gene polymorphism; cytochrome P450 3A4
• Other Study ID Numbers: CYP3A4 and sufentanil