Erythrocyte ghost – buffer partition coefficients of phenobarbital, pentobarbital, and thiopental support the pH-partition hypothesis

Abstract

The partition coefficient (λ) between red cell ghosts and buffer has been determined for three barbiturates over a range of pH. Experimental partition coefficients were linearly proportional to the calculated degree of association of the barbiturates. λ was 9.5 ± 0.52 for phenobarbital, 12.7 ± 0.91 for pentobarbital, and 27 ± 4.9 for thiopental in their acid forms. λ for all three barbiturates in their anionic forms was zero. Our data support the assumption of the pH-partition hypothesis that the dependence of λ on pH in biological membranes behaves essentially like that in organic solvents. However, the relative magnitudes of the erythrocyte partition coefficients correlate much more closely with the physiological permeability constants than do those of organic solvents, which tend to overestimate the differences between these compounds.