Cytochrome P4503A4 gene polymorphisms guide safe sufentanil analgesic doses in pregnant Chinese mothers: a multicenter, randomized, prospective study

Pharmacogenet Genomics. 2024 Jan 1;34(1):8-15. doi: 10.1097/FPC.0000000000000513. Epub 2023 Nov 14.

Abstract

Background: Sufentanil and ropivacaine when used as epidural anesthetics effectively reduce maternal pain during labor. From previous reports, rs2242480 single nucleotide polymorphisms (SNPs) can alter sufentanil metabolism, which affects analgesic efficacy.

Methods: We randomly divided 573 eligible mothers into groups A and B (in a 1 : 3 ratio). The control group (group A) was given sufentanil at the usual 0.5 mg/L-1 dose + 0.15% ropivacaine hydrochloride mixture in 10 ml. The sufentanil dose given to the intervention group (group B) was determined by genotype: the GA and AA genotype group (group B1) was given 87.6% (design based on previous study results) of the usual sufentanil clinical dose (0.438 mg/L-1 sufentanil + 0.15% ropivacaine hydrochloride mixture in 10 ml) and the GG genotype group (group B2) was given the same dose as group A. Efficacy indicators consisting of maternal vital signs, obstetric transfer, neonatal prognostic indicators, and adverse effects were recorded before and after analgesia across groups.

Results: Visual analog scale scores after analgesia across groups were significantly different from scores before analgesia, showing that analgesic effects across groups were effective. No significant differences were observed in efficacy, obstetric transfer, and neonatal prognosis indicators between groups. In comparison to groups B1 and B2, group A showed more markedly suppressed cardiovascular and respiratory effects, and also a higher incidence of negative side effects such as vomiting and urinary retention.

Conclusion: We confirmed that individualizing sufentanil doses based on maternal genotypes increased safety and success rates for women during childbirth.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Analgesia, Epidural* / methods
  • Analgesics / administration & dosage
  • Analgesics, Opioid / administration & dosage
  • Anesthetics, Local / administration & dosage
  • Cytochrome P-450 CYP3A* / genetics
  • Double-Blind Method
  • East Asian People
  • Female
  • Humans
  • Infant, Newborn
  • Polymorphism, Genetic
  • Pregnancy
  • Prospective Studies
  • Ropivacaine / administration & dosage
  • Sufentanil* / administration & dosage

Substances

  • Analgesics
  • Analgesics, Opioid
  • Anesthetics, Local
  • Ropivacaine
  • Sufentanil
  • CYP3A4 protein, human
  • Cytochrome P-450 CYP3A