The influence of age and administration rate on the brain sensitivity to propofol in rats.
BACKGROUND
It is well established that the dose of propofol for induction of anaesthesia is influenced by patient age. This may be explained by differences in pharmacokinetics or pharmacodynamics. To evaluate the effect of age on propofol pharmacodynamics, the brain concentration of propofol at the time of an EEG end-point was used as a measure of CNS sensitivity.


METHODS
Ninety-five rats were assigned to 4 groups. Anaesthesia was induced by continuous propofol infusion at different rates. The dose of propofol and duration of anaesthesia were determined from 23 up to 776 days of age. The rats were killed at 23, 287 or 776 days of age at the EEG end-point and samples of cerebral cortex, midbrain, cerebellum, serum and fat tissue were submitted to HPLC analysis of propofol concentrations.


RESULTS
The induction dose of propofol varied with age and administration rate. Young animals needed a higher dose of propofol. Old animals had higher brain concentrations of propofol at the EEG end-point than young animals. However, propofol concentrations in serum were higher in young animals. The propofol concentration in the brain was influenced by the administration rate.


CONCLUSIONS
The dose of propofol for induction of anaesthesia in rats is influenced by animal age and administration rate. Young animals need a larger induction dose than old rats, but are more sensitive as measured by the brain concentration of propofol. The larger induction dose in young rats when compared with adults is explained by pharmacokinetic differences rather than by pharmacodynamic changes.
Department of Pharmacology, Umeå University, Sweden.
J E
JE
Larsson
G
G
Wahlström
D000375:Aging / Q000502:physiology*; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D015742:Propofol