Effect of Pregnane X Receptor*1B genetic polymorphisms on postoperative analgesia with fentanyl in Chinese patients undergoing gynecological surgery.

BACKGROUND: The purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery. METHODS: A total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1'-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR * 1B haplotype was analyzed via PHASE V.2.1 software. RESULTS: The polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR * 1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes. CONCLUSIONS: PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR * 1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery. TRIAL REGISTRATION: The DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.

Effect of ABCB1 rs12720464 and rs1055302 polymorphisms in Chinese patients on the time course of action of rocuronium administered as a single dose.

OBJECTIVE: To determine whether ABCB1 gene polymorphisms affect the time course of action of rocuronium in Chinese patients. METHODS: This study included 105 unrelated Chinese patients undergoing general anesthesia with propofol, fentanyl, and rocuronium. Neuromuscular monitoring was performed with calibrated acceleromyography. Patients were allowed to recover spontaneously from the neuromuscular block. The time interval between the first maximum depression of the train of four (TOF) and spontaneous recovery TOF ratio of 0.25/0.7/0.8/0.9 was recorded. The Sequenom MassArray® single-nucleotide polymorphism (SNP) detection technology was used to detect the genotypes of the ABCB1 rs12720464, rs1055302. Demographic and non-genetic clinical data were also collected. RESULTS: In the present study, the mean time to spontaneous recovery of TOF ratio 0.8/0.9 in ABCB1 rs12720464 GG genotype was longer compared to that observed in ABCB1 rs12720464 AG genotype (56.77 ± 14.23 minutes vs. 49.50 ± 10.49 minutes, and 62.58 ± 18.16 minutes vs. 53.20 ± 12.56 minutes, respectively, p < 0.05). Further, the time to spontaneous recovery of TOF 0.7/0.8/0.9 in ABCB1 rs1055302 GG genotype was longer than that in ABCB1 rs1055302 AG genotype (52.00 ± 12.10 minutes vs. 44.83 ± 7.38 minutes, 55.96 ± 13.92 minutes vs. 46.83 ± 7.67 minutes, 61.66 ± 17.70 minutes vs. 49.50 ± 8.44 minutes, respectively, p < 0.05). CONCLUSION: In Chinese patients who were administered a single dose of rocuronium, the genetic variants ABCB1 rs12720464, and rs1055302 contribute to the individual< variability of time course of action.

CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients.

PURPOSE: This study aimed to investigate whether CYP3A4*1G genetic polymorphism influences the metabolism of fentanyl in human liver microsomes in Chinese patients. METHODS: The human liver microsomes were obtained from 88 hepatobiliary surgery patients who accepted liver resection surgery in this study. A normal liver sample (confirmed by the Department of Pathology) was taken from the outer edge of the resected tissue. The metabolism of fentanyl in human liver microsomes was studied. The concentration of fentanyl was measured by high performance liquid chromatography. The CYP3A4*1G variant allele was genotyped using the PCR restriction fragment length polymorphism method. RESULTS: The frequency of the CYP3A4*1G variant allele was 0.188 in the 88 Chinese patients who had received hepatobiliary surgery. The metabolic rate of fentanyl in patients homozygous for the *1G/*1G variant (0.85 ± 0.37) was significantly lower than that in patients bearing the wild-type allele *1/*1 (1.89 ± 0.58) or in patients heterozygous for the *1/*1G variant (1.82 ± 0.65; p < 0.05). There were no gender-related differences in the metabolic rate of fentanyl (p > 0.05) nor was there any correlation between age and metabolic rate of fentanyl (p > 0.05). Results from different hepatobiliary diseases showed no significant difference in the metabolic rate of fentanyl (p > 0.05). The difference of CYP3A4 mRNA among different CYP3A4*1G variant alleles was significant (p < 0.05). There was positive correlation between CYP3A4 mRNA and metabolic rate of fentanyl (p < 0.01). CONCLUSIONS: CYP3A4*1G genetic polymorphism decreases the metabolism of fentanyl. There is a positive correlation between CYP3A4 mRNA level and metabolism of fentanyl.