Author: Fischler M.
Publisher: Adis International
ISSN: 1173-2563
Source: Clinical Drug Investigation, Vol.18, Iss.5, 1999-11, pp. : 377-389
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Abstract
Objective: To investigate and compare the pharmacokinetic parameters of sufentanil and fentanyl during a prolonged period after single bolus administration, 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 35 years, undergoing coronary artery bypass graft surgery, were randomised to anaesthesia with sufentanil/O (n = 20) or fentanyl/O (n = 21).Methods: Arterial blood samples were taken up to 24 hours after administration for determination of plasma opioid concentrations, and haemodynamic parameters were monitored during and after the surgical procedure. Pharmacokinetic data were analysed by compartmental analysis and by population analysis 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) of fentanyl was 20.7 hours, total body clearance (CL) was 4.7 ml/min/kg and volume of distribution at steady state (V) was 5.2 L/kg. For sufentanil, t was 37.7 hours, CL was 7.4 ml/min/kg and V was 13.9 L/kg. No correlation was observed between demographic data and pharmacokinetic parameters for sufentanil, whereas for fentanyl significant correlations were revealed between age and V, t and the intercompartmental transfer rate constant k. 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 receiving sufentanil (p = 0.02).Conclusions: Our study allowed a better determination of the pharmacokinetic parameters of high-dose sufentanil administered as a single bolus, and we demonstrated a clear pharmacokinetic difference between fentanyl and sufentanil in terms of higher CL and larger V for sufentanil. These pharmacokinetic differences have not had clinically relevant consequences in our study. 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.
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