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.

Salicylate pharmacokinetics in the dog at 6 ATA in air and at 2.8 ATA in 100% oxygen.

Hyperbaric air and hyperbaric hyperoxia, which have been shown to decrease both liver plasma flow and plasma volume in dogs, may potentially affect the disposition of drugs whose distribution and/or elimination are dependent upon those actions. This study examined the effects of those conditions on the disposition of salicylic acid, using the dog as a model. The drug was administered to six mixed-breed dogs as a 10 mg sodium salicylate/kg i.v. bolus at 1 ATA breathing air (control), at 2.8 ATA breathing 100% O2, and at 6 ATA breathing air, followed by serial blood sampling for 8 h. Statistical analysis showed a significant increase (p less than 0.05) in salicylate clearance at 2.8 ATA compared to control with a subsequent, although not statistically significant, increase in elimination half-life. There were no significant differences between the values observed at 6 ATA and either control or 2.8 ATA. As 100% O2 at 2.8 ATA is used during hyperbaric oxygen medical therapy and during decompression, this change in disposition of this commonly used agent may have implications in man. Studies in man must be conducted, however, to determine if the same conclusions apply.

Hemodynamic effects of lactated Ringer's solution on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia.

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After allowing 5-7 d for recovery the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg) and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. Enough lactated Ringer's solution was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. There were statistically significant differences in some of the measured parameters due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of lactated Ringer's solution.

Theophylline pharmacokinetics during hyperbaria and hyperbaric hyperoxia in the dog.

The effect of hyperbaria and hyperbaric hyperoxia on the disposition kinetics of theophylline were investigated in the dog. The drug was administered as a 5 mg/kg iv bolus at 1 atmospheres absolute (ATA), 2.8 ATA and 6 ATA. Serial blood samples were collected over an eight hour period and analyzed for theophylline concentration using a gas chromatographic method. From the resultant data, elimination half-life, volume of distribution and total body clearance were calculated. There were no apparent effects of hyperbaria or hyperbaric hyperoxia on any of the parameters describing theophylline disposition, implying that, in the animal model studied, distribution, elimination and effect should remain constant.