Pharmacodynamics and pharmacokinetics of propofol in a medium-chain triglyceride emulsion.
BACKGROUND
Because propofol is water insoluble, current formulations of propofol use a soybean oil emulsion. These soybean emulsions cause elevated plasma triglycerides and support bacterial growth. This study compares an alternative formulation of propofol as a 2% emulsion in a medium-chain triglyceride solution (IDD-D Propofol) with Diprivan.


METHODS
This double-blind, crossover, phase 1 study compared IDD-D Propofol with Diprivan using two consecutive protocols of 12 subjects each. Subjects in protocol 1 received a single bolus of 2.5 mg/kg, and those in protocol 2 received the same induction dose followed by a 30-min infusion at 0.2 mg. kg(-1).min(-1). Venous samples were taken for propofol concentration and biochemical measurements. Induction and emergence times were measured by termination of voluntary counting and responding to command, respectively.


RESULTS
Plasma concentrations were not different between the two formulations. Induction time was 14% longer with IDD-D Propofol than with Diprivan (N = 24, protocols 1 and 2 combined, 53.3 +/- 12.1 s and 46.9 +/- 7.8 s, respectively; P = 0.002). Emergence time was not significantly different for protocol 1 but was marginally longer (P = 0.04) for IDD-D Propofol in protocol 2 (1,197 +/- 445 s [n = 11] and 1,254 +/- 468 s [n = 12], respectively). As expected because of the inherent characteristics of the formulations, plasma triglycerides were elevated for Diprivan but not for IDD-D Propofol; octanoate, a metabolite of medium-chain triglycerides, was elevated only with IDD-D Propofol. Octanoate was elevated to concentrations below those considered toxic. Plasma concentrations of other biochemical markers of medium-chain triglyceride metabolism, ketones, showed no significant changes. Interestingly, there were significant differences between male and female subjects in the propofol plasma concentrations and time to awakening with both drugs.


CONCLUSIONS
Differences between the two propofol formulations were slight and not clinically significant. Similar gender differences in plasma concentrations and awaking times were found for both formulations.
Ward
Denham S
DS
Department of Anesthesiology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 604, Rochester, NY 14642, USA. Denham_Ward@URMC.Rochester.edu
Norton
J Russell
JR
Guivarc'h
Pol-Henri
PH
Litman
Ronald S
RS
Bailey
Peter L
PL
D000328:Adult; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004655:Emulsions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D014280:Triglycerides
D018686:Anesthetics, Intravenous; D004655:Emulsions; D014280:Triglycerides; D015742:Propofol