Association of CYP3A4 rs2242480 With Sufentanil Plasma Concentration and PCA Consumption

Study Overview
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Brief Summary
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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
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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

Official Title
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Association of CYP3A4 rs2242480 With Sufentanil Plasma Concentration and PCA Consumption

Conditions
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Surgery, Individuality

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| rs2242480 wild-type homozygote<br>*1/*1 Grouped by rs2242480 polymorphism genotyping | |
| rs2242480 mutant heterozygote<br>*1/*1G Grouped by rs2242480 polymorphism genotyping | |
| rs2242480 mutant homozygote<br>*1G/*1G Grouped by rs2242480 polymorphism genotyping | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sufentanil, metabolism, cytochrome P450 3A4, gene polymorphism