Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil*

Abstract

SummaryWe compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan Ò 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg )1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan Ò . Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced.

The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan®at clinical and supraclinical doses

“…Therefore, knowledge of the pharmacokinetic variables of alfaxalone will be useful as an aid in the design of dose regimens especially for animals with known departures from physiological normality. Further, it is well known that formulation characteristics may affect the pharmacokinetics of anaesthetic drugs (Dutta & Ebling, 1997; Paul et al. , 2003).…”

Transient phlebitis induced by a bolus injection of propofol

“…The incidence of thrombophlebitis induced by propofol (Diprivan) as a 1% solution in an aqueous solution of 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide is reportedly less than 6.6% [1,2]. However, the incidence of propofol-induced transient phlebitis is still unclear, although a previous study documented that the incidence of phlebitis without thrombosis at the end of the surgery is 0.4% [3].…”

Novel propofol derivatives and implications for anesthesia practice

“…Clinical trials for this agent were also discontinued in 1999. [24] Propofol-Lipuro ® is another mixed MCT–LCT propofol formulation. The emulsion did not affect the pharmacokinetics or pharmacodynamics of propofol, caused less pain upon injection, and increased speed of triglyceride elimination.…”