Pharmacokinetics and pharmacodynamics of propofol in a new solvent.
Pain on injection is the most commonly reported adverse event after propofol injection. In a randomized, cross-over study in two groups of 12 healthy male volunteers (24-42 yr), we compared the pharmacokinetics and pharmacodynamics of two new propofol formulations (1% and 2% concentrations) in a fat emulsion consisting of medium- and long-chain triglycerides with the standard propofol formulation. After a single intravenous bolus injection of 2 mg/kg, propofol blood levels were measured for 24 h and evaluated according to an open three-compartment model. The derived pharmacokinetic variables were not different among formulations. Additionally, electroencephalographic recordings of the onset and duration of hypnotic action were comparable with all formulations. After propofol 1% in the new formulation, fewer volunteers reported severe or moderate pain on injection (9%) than after the standard formulation (59%) (P < 0.05). We attribute this result to a lower concentration of free propofol in the aqueous phase of the new formulation.


CONCLUSIONS
Changing the composition of the carrier fat emulsion for propofol does not have an impact on the pharmacokinetics and efficacy of propofol, but it promises to provide better patient acceptance by lowering the incidence of moderate and severe pain on injection.
Doenicke
A W
AW
Institute of Anesthesiology, University of Munich, Germany.
Roizen
M F
MF
Rau
J
J
O'Connor
M
M
Kugler
J
J
Klotz
U
U
Babl
J
J
D000328:Adult; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004338:Drug Combinations; D004569:Electroencephalography; D005217:Fat Emulsions, Intravenous; D006801:Humans; D007275:Injections, Intravenous / Q000009:adverse effects; D008297:Male; D010146:Pain / Q000209:etiology; D010743:Phospholipids; D015742:Propofol / Q000009:adverse effects / Q000493:pharmacokinetics*; D012890:Sleep / Q000187:drug effects; D013012:Sorbitol
D018686:Anesthetics, Intravenous; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; C008288:Lipofundin; D013012:Sorbitol; D015742:Propofol