Binding of non-steroid anti-inflammatory drugs and warfarin to liver tissue of rabbits in vitro

Liver slices (10mm 0.1mm thickness) were incubated at 37 degrees C in drug solutions up to 360 min. The drugs were dissolved in Ringer solution of pH 7.0. After 60, 180, 240 and 360 min each drug concentration was determined in the incubation fluid. For all drugs tested equilibrium was obtained after 240 min. The amount of drug taken up by the slices was calculated from the difference to initial concentration. In parallel, samples of the slices were homogenized together with their incubation fluids after the same incubation intervals. The free concentration was determined by ultrafiltration. For warfarin and several non-steroid anti-inflammatory drugs (NSAID), i.e. acetylsalicylic acid, ibuprofen, ketoprofen and oxyphenbutazone, there was no difference between the free drug concentrations in the homogenized and in non-homogenized samples. This suggests that the binding of these drugs to liver tissue was not altered by homogenization. Further was studied whether NSAIDS interfere with binding of warfarin to liver tissue. Acetylsalicylic acid, flurbiprofen, ibuprofen, ketoprofen, oxyphenbutazone and proquazon markedly increased the free concentration of warfarin both in liver slices and homogenates (p less than 0.01). The extent of displacement did not differ between slices and homogenates.