Impact of CYP3A4*1G Polymorphism on Fentanyl Analgesia Assessed by Analgesia Nociception Index in Chinese Patients Undergoing Hysteroscopy

Abstract

Background:The clinical efficacy of fentanyl for pain control differs greatly across individuals. The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI).Methods:A total of 200 gynecologic patients scheduled for elective hysteroscopy under general anesthesia at Peking University People's Hospital from May to December in 2017 were enrolled in this study. Venous blood was withdrawn for genotyping of CYP3A4*1G before operation. Fentanyl 1 μg/kg was administered preoperatively followed by target-controlled infusion of propofol for induction and maintenance. Intraoperative analgesic efficacy of fentanyl was assessed by ANI monitoring at T0 (entering room), T1 (cervical dilation), T2 (start of cervical aspiration), and T3 (end of cervical aspiration) time points. The duration of propofol infusion and total dosage of propofol were recorded as well.Results:The patients were divided into three groups according to CYP3A4*1G polymorphism, including 143 in GG group, 47 in GA group, and 10 in AA group. There was no significant difference in clinical demographics among three groups. The frequency of CYP3A4*1G variant alleles accounted for 16.8% and the distribution of variant alleles was consistent with Hardy–Weinberg equilibrium. Using a multilevel model, ANI values at T1 (63.81 ± 19.61), T2 (63.63 ± 17.82), and T3 (65.68 ± 17.79) were significantly lower than that at T0 (77.16 ± 12.93) in the study population (F = 23.50, P < 0.001), suggesting that higher levels of pain at T1, T2, and T3 than T0. Patients with GG genotype showed significantly lower ANI than those with GA or AA genotypes during hysteroscopy under the same dose of fentanyl.Conclusion:CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesthesia.

Efficacy of Different Preemptive Analgesia on Postoperative Analgesia, Oxidative Stress, and Inflammatory Response after Gynecological Laparoscopic Surgery

“…In clinical practice, in order to relieve postoperative pain and inflammation, analgesic measures are usually taken before the injury acts on the body. is treatment is clinically called preemptive analgesia [15]. Oxycodone, as an opioid μ and κ double receptor agonist, took effect 2 min after intravenous injection and peaked at 5 min, lasting for about 3.5 h, without causing histamine release and bradycardia, or inhibiting the parasympathetic nerve, thus exerting a better inhibitory effect on visceral pain [16,17].…”

Effect of CYP3A5 and CYP3A4 Genetic Variants on Fentanyl Pharmacokinetics in a Pediatric Population

“…Fentanyl is known to be metabolized by Cytochrome P450 (CYP) enzymes, CYP3A4 and CYP3A5. Specifically CYP3A4*1G, CYP3A5*3, and CYP3A5*6 alleles have been shown to affect fentanyl PKs in adults, [9][10][11][12][13][14] although not all studies have reported significant effects. 15 Fentanyl clearance is reduced in neonates and rapidly matures in the first month of life, 16 likely due in part to the maturation of CYP3A encoded enzymes.…”

Effective Doses of Nalbuphine Combined with Propofol in Painless Hysteroscopy

“… 1 Propofol alone or combined with opioid μ receptor agonists, such as fentanyl and sufentanil, are current the anesthetic methods used for painless hysteroscopy. 6 , 7 However, propofol has a weak analgesic effect and injection pain, 8 while opioid μ receptor agonists are associated with an increased risk of respiratory depression, nausea and vomiting, 9 which are unexpected for both patients and anesthesiologists. Therefore, the anesthetic strategies still need to be improved.…”