Concentration-EEG effect relationship of propofol in rats

J Pharm Sci. 1997 Jan;86(1):37-43. doi: 10.1021/js960247n.

Abstract

Propofol is a unique highly lipid-soluble anesthetic that is formulated in a fat emulsion (Diprivan) for intravenous (i.v.) use. It has the desirable properties of rapid onset and offset of effect following rapid i.v. administration and minimal accumulation on long-term administration. Based on physicochemical properties and preliminary brain solubility data, propofol should have an extended effect-site turnover and a resulting prolonged effect. However, a preliminary study in humans has reported a rapid blood-brain equilibration half-time (T1/2 kE0) of only 2.9 min. We used a chronically instrumented rat model to examine the unique disposition and electroencephalographic (EEG) pharmacodynamics of propofol. Although the pharmacokinetics were variable, there was low interindividual variability in the concentration-EEG effect relationship. The duration of EEG sleep was 26 (+/- 44% CV) min following 11-15 mg/kg doses of propofol. The T1/2 kE0 was 1.7 (+/- 32%) min. Apparent effect-site concentrations of 0.5-1 microg/mL were required to maintain sleep in rats. Like other general anesthetics, the concentration-EEG effect relationship of propofol is biphasic. At a propofol concentration of 0.6 (+/- 35%) microg/mL, the number of EEG waves/s was maximal at 175% of baseline awake state. Further increases in the concentration of propofol depressed EEG activity until complete suppression occurred at 7 (+/- 22%) microg/mL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Intravenous / blood
  • Anesthetics, Intravenous / pharmacokinetics
  • Anesthetics, Intravenous / pharmacology*
  • Animals
  • Blood-Brain Barrier
  • Chromatography, High Pressure Liquid
  • Electrochemistry
  • Electroencephalography
  • Male
  • Propofol / blood
  • Propofol / pharmacokinetics
  • Propofol / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Anesthetics, Intravenous
  • Propofol