Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat

We evaluated the pharmacokinetics and regional distribution of propofol in the brain and spinal cord during propofol anesthesia in Sprague-Dawley rats, using high-performance liquid chromatographic determination of propofol concentration in brain, whole blood and plasma. We found that the concentration of propofol in the brain increased and decreased expeditiously during and after a 15-min and 30-min period of i.v. infusion of an anesthetic dose (60 mg/kg per h) of propofol. Furthermore, propofol was evenly distributed in the brain and spinal cord during infusion, with a significant inter-individual variation. Upon the establishment of anesthesia 15 and 30 min following intravenous infusion of propofol, the concentration of propofol in the brain, whole blood and plasma was respectively 15.7 +/- 1.9 and 39.4 +/- 2.7 micrograms/g, 4.5 +/- 1.2 and 13.6 +/- 1.3 micrograms/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 micrograms/ml (mean +/- SEM, n = 6 or 7). These high brain/blood and brain/plasma ratios during anesthesia suggest that propofol manifests a pharmacokinetic profile that is different from at least thiopental.

[1]  P. White,et al.  Propofol: An update on its Clinical Use , 1994, Anesthesiology.

[2]  T. Gin.  Pharmacodynamics of propofol and free drug concentrations. , 1993, Anesthesiology.

[3]  R James,et al.  Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents. , 1980, Journal of medicinal chemistry.

[4]  J. Kendig,et al.  Propofol and barbiturate depression of spinal nociceptive neurotransmission. , 1992, Anesthesiology.

[5]  E. Gepts,et al.  Pharmacokinetic Implications for the Clinical Use of Propofol , 1989, Clinical pharmacokinetics.

[6]  T. B. Kuo,et al.  Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous bolus administration , 1993, Neuroscience Letters.

[7]  E. J. Douglas,et al.  Distribution in female rats of an anaesthetic intravenous dose of 14C-propofol. , 1991, Xenobiotica; the fate of foreign compounds in biological systems.

[8]  C. Hug.  Pharmacokinetics of Drugs Administered Intravenously , 1978, Anesthesia and Analgesia.

[9]  A. Burm,et al.  Pharmacodynamics of propofol in female patients. , 1992, Anesthesiology.

[10]  E Kochs,et al.  The effects of propofol on cerebral and spinal cord blood flow in rats. , 1993, Anesthesia and analgesia.

[11]  Power spectral analysis of the electroencephalographic and hemodynamic correlates of propofol anesthesia in the rat: Intravenous infusion , 1993, Neuroscience Letters.

[12]  C. Porro,et al.  Brain and spinal cord metabolic activity during propofol anaesthesia. , 1991, British journal of anaesthesia.

[13]  S. Roth,et al.  Plasma, Brain, and Spinal Cord Concentrations of Thiopental Associated with Hyperalgesia in the Rat , 1994, Anesthesiology.

[14]  T. Vree,et al.  High-performance liquid chromatographic determination and preliminary pharmacokinetics of propofol and its metabolites in human plasma and urine. , 1987, Journal of chromatography.