Modifications of clonidine binding to rabbit liver protein under the influence of non-steroid-anti-inflammatory drugs in vitro.

This study was designed to investigate the binding of clonidine to liver protein as well as the possible interactions with non-steroid anti-inflammatory drugs (NSAIDs) during the binding process in the rabbit. The binding of clonidine to slices (S) and homogenized slices (H) was estimated by a radioisotopic method following incubation with a mixture of cold and 3H-labelled clonidine in Ringer solution at 37 degrees C for 360 min. The binding of clonidine was assessed in the absence and presence of the following NSAIDs: flurbiprofen, ketoprofen, ibuprofen and acetylsalicylic acid. The results showed that the percentage of clonidine binding did not differ between intact and homogenized slices. The addition of all NSAIDs but ibuprofen, significantly decreased the protein binding of clonidine both in intact and homogenized liver slices. This finding could be attributed to the different affinity of ibuprofen for liver protein compared to the remaining NSAID's which may arise from a number of chemical properties including its dual Pka values.