Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery

Objective: A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (prop ofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during prolonged infusions of propofol. The phar macokinetics, pharmacodynamics and safety characteristics of propofol 6% SA ZN were investigated during a short-term infusion and compared with the com mercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). Methods: In a randomised double-blind study, 24 male patients received a 5- h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immedia te postoperative period following coronary artery bypass surgery. Results: The average pharmacokinetic parameter estimates of clearance (Cl), volume of distribution at steady state (V-d,V-ss), elimination half-life ( t(1/2,beta)) and distribution half-life (t(1/2,alpha)) observed in the thre e groups were 28 +/- 1.1 ml/kg/min, 1.8 +/- 0.12 l/kg, 94 +/- 4.1 min and 3 .1 +/- 0.26 min, respectively (mean +/- SEM, n = 24) and no significant dif ferences were noted between the three formulations (P > 0.05). In one patie nt receiving propofol 6% SAZN, in two patients receiving propofol 1% SAZN a nd in three patients receiving Diprivan-10, the level of sedation was inade quate and additional sedative medication had to be given. In all other 18 p atients, the level of sedation was adequate. The mean propofol concentratio n in these six inadequately sedated patients was lower than the adequately sedated patients (P = 0.015). The serum triglyceride concentrations were no t significantly different between the groups studied. No adverse events occ urred in any of the patients. Conclusions: The pharmacokinetics, pharmacodynamics and safety characterist ics of propofol 6% SAZN are in good agreement with those of the 1% formulat ions. Propofol 6% SAZN therefore provides a useful alternative to the comme rcially available 1% formulation for short-term sedation in the intensive c are unit. Expected advantages in long-term sedation of the 6% over 1% formu lation are the subject of an ongoing study.