Comparative pharmacokinetic study of fentanyl and sufentanil after single high-bolus doses

Objective: To investigate and compare the pharmacokinetic parameters of suf entanil and fentanyl during a prolonged period after single bolus administr ation and to detect and compare the occurrence of secondary peaks of opioid plasma concentration. Design: This was a prospective, double-blind, randomised study in surgical patients. Patients: Forty-one patients, aged greater than or equal to 35 years, under going coronary artery bypass graft surgery, were randomised to anaesthesia with sufentanil/O-2 (n = 20) or fentanyl/O-2 (n = 21). Methods: Arterial blood samples were taken up to 24 hours after administrat ion for determination of plasma opioid concentrations, and haemodynamic par ameters were monitored during and after the surgical procedure. Pharmacokin etic data were analysed by compartmental analysis and by population analysi s using a nonlinear mixed-effect modelling approach Results: There were no significant differences in demographics, features of the surgical procedure or haemodynamic parameters between the two groups. By population analysis, the terminal elimination half-life (t(1/2)z) of fen tanyl was 20.7 hours, total body clearance (CL) was 4.7 ml/min/kg and volum e of distribution tion at steady state (V-SS) was 5.2 L/kg. For sufentanil, t(1/2)z was 37.7 hours, CL was 7.4 ml/min/kg and V-SS was 13.9 L/kg. No co rrelation was observed between demographic data and pharmacokinetic paramet ers for sufentanil, whereas for fentanyl significant correlations were reve aled between age and V-SS, t(1/2)z and the intercompartmental transfer rate constant k(21). Significant differences were observed in the occurrence of secondary peaks, which occurred in nine patients receiving fentanyl (with two patients exhibiting double secondary peaks) and in one patient receivin g sufentanil (p = 0.02). Conclusions: Our study allowed a better determination of the pharmacokineti c parameters of high-dose sufentanil administered as a single bolus, and we demonstrated a clear pharmacokinetic difference between fentanyl and sufen tanil in terms of higher CL and larger V-SS for sufentanil. These pharmacok inetic differences have not had clinically relevant consequences in our stu dy. However, the occurrence of secondary peaks, which have been considered as a risk factor in the postoperative period, is significantly reduced with sufentanil compared with fentanyl.