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The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in patients submitted to elective surgeries

A C C Costa1, E B Coelho2, V L Lanchote1

  • 1Universidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

European Journal of Clinical Pharmacology
|April 15, 2017
PubMed
Abstract

Insights

Genetic variations in the SLCO1A2 gene, specifically the -189_-188InsA polymorphism, impact how the body processes rocuronium. This finding is crucial for understanding rocuronium pharmacokinetics in patients undergoing surgery.

Area of Science:

  • Pharmacogenomics
  • Drug Metabolism
  • Clinical Pharmacology

Background:

  • Rocuronium (ROC) is a neuromuscular blocker primarily eliminated via biliary excretion.
  • This excretion is dependent on hepatocellular uptake by organic anion transporting polypeptide 1A2 (OATP1A2).
  • The influence of genetic variations in SLCO1A2, the gene encoding OATP1A2, on ROC pharmacokinetics remains uncharacterized.

Purpose of the Study:

  • To investigate the impact of SLCO1A2 genetic polymorphisms on the pharmacokinetics of rocuronium (ROC).
  • To evaluate the relationship between specific SLCO1A2 variants and ROC clearance in surgical patients.

Main Methods:

  • Genotyping of patients undergoing elective surgery for SLCO1A2 polymorphisms in coding and promoter regions.
  • Pharmacokinetic parameters of rocuronium were determined using non-compartmental analysis.
  • Analysis included common variants and a novel insertion polymorphism (-189_-188InsA).

Main Results:

  • No significant association was found for most tested SLCO1A2 polymorphisms.
  • A linkage disequilibrium was observed between -1105G>A and -1032G>A genotypes.
  • Patients with the SLCO1A2 -189_-188InsA polymorphism (n=17) exhibited reduced ROC total clearance compared to wild-type (n=13) (151.6 vs 207.1 mL/min, p≤0.05).

Conclusions:

  • The SLCO1A2 -189_-188InsA polymorphism is associated with reduced rocuronium clearance.
  • This finding has implications for personalized anesthesia management in patients with this genetic variant.
  • Further research is warranted to elucidate the precise mechanisms of OATP1A2 in ROC disposition.
Keywords:
Neuromuscular blockadePharmacogeneticsPharmacokineticsRocuroniumSNPs

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