Premium
Behavioral Effects and Pharmacokinetics of Propofol in Rats Selected for Differential Ethanol Sensitivity
Author(s) -
Liu Yong,
Fay Tina,
Deitrich Richard A.
Publication year - 1995
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1995.tb00961.x
Subject(s) - propofol , pharmacokinetics , isoflurane , pentobarbital , anesthesia , anesthetic , ethanol , halothane , arterial blood , pharmacology , medicine , chemistry , biochemistry
High‐ and low‐alcohol sensitivity (HAS and US) rats have been selected for their differences in ethanol‐induced sleep time. The rats also differ in sensitivity to pentobarbital, halothane, isoflurane, and enflurane. To determine if this sensitivity extended to propofol, the anesthetic requirements were measured. In this study, the sleep time and the tissue levels of propofol at awakening, as well as the pharmacokinetics, were evaluated. Propofol was administered intravenously. For one group of rats, sleep times were measured; blood and brain samples were taken at awakening. Blood samples were collected in another group of rats at frequent Intervals from 0 to 90 min after Injection. Propofol concentration of the samples was determined by gas chromatography. The pharmacokinetic analysis was performed using a nonlinear least‐squares regression program. Sleep time was not different; however, blood and brain propofol levels at awakening showed a small, but significant difference between HAS and IAS rats. Propofol blood concentration‐time curve data were fitted to a three‐compartment model. Pharmacokinetic parameters were also not different between the rat lines. However, sleep time was 50% longer in female rats than male rats in both strains ( p < 0.0001). The rates of propofol clearance were slower in female rats, because of different rates of disappearance from the second compartment. The observations suggest that the genetic selection for ethanol sensitivity selection for propofol sensitivity was not nearly as intense and presumably involves some different genes. These two central nervous system dressings would seem to differ significantly in their mechanism of action. The differential sleep times produced by propofol in the male and female rats are caused by pharmacokinetic differences.