Pharmacokinetics of pentobarbital under hyperbaric and hyperbaric hyperoxic conditions in the dog

High hydrostatic pressure has been shown to reverse the anesthetic effects of barbiturates. However, attempts to distinguish between two possible causes of this reversal, changes in drug disposition or changes in drug-receptor interaction, have not been reported. This study examined the possible effects of hyperbaria and hyperbaric hyperoxia on the distribution and clearance of pentobarbital in the dog. The drug was administered to six mixed-breed dogs as a 30 mg/kg i.v. bolus at 1 ATA breathing air, 6 ATA breathing air, and 2.8 ATA breathing 100% oxygen, with serial blood sampling for 12 h. Pharmacokinetic and statistical analyses showed no significant effects of hyperbaria or hyperbaric hyperoxia on the total plasma clearance, volume of distribution or elimination half-life. If pressure reversal of barbiturate anesthesia occurs at these pressures, changes in the disposition of the drug are not the causative factors.