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 mu g/g, 4.5 +/- 1.2 and 13.6 +/- 1.3 mu g/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 mu g/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.