Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients

Abstract

Background Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23–76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples (1.5 ml) were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters: the central volume of distribution (V1) = 5.4 L, the volume of distribution at steady-state (Vdss) = 195.4 L, systemic clearance (Cl1) = 1.10 L/min, and elimination half-life (t1/2 γ) = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance (Cl2) was negatively correlated with patient age, and the volume of slowly equilibrating compartment (V3) was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment (V2) were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.