EFFECT OF NEPHRECTOMY ON THE DURATION OF SLEEP FOLLOWING ADMINISTRATION OF THIOPENTAL AND HEXOBARBITAL

¹ Department of Pharmacology, Abbott Laboratories, North Chicago, Illinois

1. Bilateral nephrectomy does not (or only slightly) change the duration of sleep following an immediate intravenous hexoharbital or thiopental injection in rats or rabbits. When three or more hours are allowed to pass after nephrectomy the duration of the thiopental effect becomes markedly prolonged in both species, while hexobarbital shows only a moderate prolongation in rats but not in rabbits.

2. The degree of the increased thiopental effect has been shown in rats to be in linear relation to the time after nephrectomy and the increase of the plasma NPN level. Ligation of the ureters leads to similar, but less marked effects upon thiopental sleep.

3. The duration of action of a threshold dose of thiopental is not or only slightly affected by nephrectomy.

4. If the NPN plasma level is raised acutely in freshly nephrectomized animals by the injection of an artificial NPN solution, an immediate increase of sensitivity to thiopental appears in these, but not normal animals. Sodium chloride or dextrose in amounts equi-osmotic to the NPN solution produce a similar but less pronounced effect.

5. Analytical studies indicate that the fall of the barbiturate plasma level during the "normal" sleep period is the same in control and nephrectomized animals. However, from then on the drop is significantly slower in the operated animals. It appears that the post-nephrectomy state is associated with a somewhat greater sensitivity to the drug and a slower metabolic degradation of it.