The "ultra-free" ultrafiltration technique compared with equilibrium dialysis for determination of unbound thiopental concentrations in serum.

We compare a new ultrafiltration technique, involving a unique Millipore membrane, with the classical method of equilibrium dialysis for determining the fraction of thiopental not bound to serum proteins. This fraction, as determined by equilibrium dialysis at 37 degrees C, ranged between 12 and 16% for total concentrations at 50 microgram/L to 10 mg/L of serum. In contrast, ultrafiltration at 37 degrees C yielded a 49% higher value for unbound thiopental: 26.3 (SD 2.6)%. Determined at room temperature (24 degrees C), there was no statistically significant difference for results by the two methods: 14.2 and 15.9%, respectively. The discrepancy between results at 37 degrees C may partly be explained by serum proteins penetrating the Ultra-Free filter. For the routine clinical measurement of unbound drug concentrations, the ultrafiltration membrane at room temperature appears to be sufficiently accurate and less time-consuming than equilibrium dialysis.