Effect of CYP2B6 and UGT1A9 Genotypes on Differences in Predicted and Measured Propofol Concentrations after Propofol Anesthesia

Abstract

Propofol is widely used for general anesthesia administered by manually controlled infusion (MCI) or target-controlled infusion (TCI). Multi-compartment pharmacokinetic models, such as The Marsh or Schnider model are used by TCI systems to calculate the infusion rates required to achieve the target concentration (plasma or effect-site concentration). However, several reports indicated a difference between predicted blood propofol concentration (Cp) and measured blood propofol concentration (Cm). We investigated whether genetic polymorphisms of cytochrome P450 2B6 (CYP2B6) and UDP-glucuronosyltransferase 1A9 (UGT1A9) can influence the difference between Cp and Cm using prediction error (PE) of propofol anesthesia.
Between June 2009 and May 2011, 89 patients (48 males,41 females) who underwent respiratory surgery with total intravenous anesthesia were examined. Arterial blood samples were collected at 0, 5, 10, 20, 30, and 60 min after the termination of propofol infusion for the determination of Cm and genetic polymorphisms of CYP2B6 and UGT1A9. We calculated Cp with the TIVA trainer® using the Marsh and Schnider models at 0, 5, 10, 20, 30, and 60 min after the termination of propofol infusion.
There was a significant difference in PE in the Marsh model, immediately after propofol infusion for CYP2B6 (p=0.042), but there was no significant difference in PE in the Schnider model. Our results suggested that the polymorphism of CYP2B9 may affect the difference in TCI in the Marsh model, but not in the Schnider model. However, the results also suggest that there is no clinical usefulness of this statistical difference in anesthetic management.