PLASMA BINDING OF THIOPENTAL IN THE NEPHRECTOMIZED RABBIT

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

1. Thiopental in the ultra-filtrate of rabbit plasma was determined in normal and post-nephrectomy rabbits. It was found that normal rabbit plasma bound 75 per cent of the thiopental in physiological concentrations. Twenty-four hours after nephrectomy only 65 per cent was bound in the same rabbit.

2. Although the nephrectomized rabbits slept longer than the controls, they awoke with a higher total plasma concentration. However, the level of thiopental in the ultra-filtrate was not significantly different.

3. Nephrectomy decreased the in vitro as well as the in vivo binding in anesthetic concentrations of thiopental. Binding by normal plasma was not influenced in vitro by the addition of large amounts of urea.

4. While total protein and the hematocrit values were not influenced by nephrectomy a slight drop in albumin from 3.58 to 3.13 gm./100 ml. plasma was detected with a concomitant increase in some of the other plasma protein fractions.

5. The prolongation of sleeping time following nephrectomy was shown by thiopental, pentobarbital, Ortal and Pernoston, but not by Evipal and Ipral. There was a positive correlation between human and bovine serum albumin binding and prolongation of sleeping time in the post-nephrectomy rabbit.