Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil.
We 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 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. 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.
Paul
M
M
Department of Anaesthesia, University of Cologne, Joseph-Stelzmann-Str. 31, 50931 Cologne, Germany. M.Paul@uni-koeln.de
Dueck
M
M
Kampe
S
S
Fruendt
H
H
Kasper
S M
SM
D000328:Adult; D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000097:blood*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005079:Excipients; D006801:Humans; D008297:Male; D010146:Pain / Q000139:chemically induced; D015742:Propofol / Q000009:adverse effects / Q000097:blood*; D013024:Soybean Oil; D013924:Thrombophlebitis / Q000139:chemically induced*
D018686:Anesthetics, Intravenous; D005079:Excipients; D013024:Soybean Oil; D015742:Propofol