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Pharmacodynamics and pharmacokinetics of propofol in a medium-chain triglyceride emulsion
Denham S Ward1, J Russell Norton, Pol-Henri Guivarc'h
1Department of Anesthesiology, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box 604, Rochester, NY 14642, USA. Denham_Ward@URMC.Rochester.edu
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.
Insights
This study found that IDD-D Propofol, an alternative propofol formulation, had slight differences in induction and emergence times compared to Diprivan. IDD-D Propofol did not elevate plasma triglycerides, unlike Diprivan.
Area of Science:
- Anesthesiology
- Pharmacology
- Drug Formulation
Background:
- Current propofol formulations use soybean oil emulsions, leading to elevated plasma triglycerides and supporting bacterial growth.
- An alternative propofol formulation, IDD-D Propofol (2% emulsion in medium-chain triglyceride solution), was developed to address these issues.
Purpose of the Study:
- To compare the safety and efficacy of IDD-D Propofol with the standard formulation, Diprivan.
- To evaluate propofol plasma concentrations, induction and emergence times, and biochemical markers.
Main Methods:
- A double-blind, crossover, phase 1 study involving 24 subjects across two protocols.
- Subjects received either a single bolus or a bolus followed by a 30-minute infusion of IDD-D Propofol or Diprivan.
- Measurements included propofol plasma concentrations, induction/emergence times, and biochemical parameters.
Main Results:
- No significant differences in propofol plasma concentrations between the two formulations.
- IDD-D Propofol showed a 14% longer induction time (P = 0.002) and marginally longer emergence time in one protocol (P = 0.04).
- Diprivan elevated plasma triglycerides, while IDD-D Propofol elevated octanoate to non-toxic levels; other biochemical markers remained unchanged. Significant gender differences were observed.
Conclusions:
- The differences between IDD-D Propofol and Diprivan were minor and not clinically significant.
- Both formulations exhibited similar gender-related variations in plasma concentrations and awakening times.
- IDD-D Propofol offers an alternative formulation without the triglyceride-elevating effects of soybean oil emulsions.