Albumin as a potential membrane transport barrier for hepatic clearance of diazepam studied by a universal organ clearance approach.

Published data on the effect of albumin binding on hepatic extraction of diazepam in isolated perfused rat livers were analyzed by a simple universal organ clearance approach proposed earlier by this author. Apparent hepatic intrinsic clearance of free (unbound) diazepam was found to decrease 39-fold from 334 ml/min in the absence of albumin to only 8.6 ml/min when the fraction unbound was reduced to 0.052. This interesting finding is rationalized by adsorption of albumin onto the surface of liver cells which might temporarily bind the drug molecules and slow down their diffusion across the membrane. A term "relative permeability" was introduced.