Association of CYP3A4 rs2242480 With Sufentanil Plasma Concentration and PCA Consumption

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02070614

Enrollment

Registered

2014-02-25

Start date

2013-12-31

Completion date

2014-05-31

Last updated

2015-09-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Individuality, Surgery

Keywords

sufentanil, metabolism, cytochrome P450 3A4, gene polymorphism

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

Interventions

None listed

Study design

Observational model

COHORT

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

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

Countries

China

Outcome results