DECREASE IN PENBUTOLOL CENTRAL RESPONSE AS A CAUSE OF CHANGES IN ITS SERUM-PROTEIN BINDING

Abstract— Penbutolol is a β‐adrenoceptor antagonist that is extensively bound to α1‐acid glycoprotein (α1‐AGP), a protein that increases in inflammatory diseases thereby binding more drug in such conditions. Changes in serum binding can lead to modifications in the pharmacokinetics and pharmacodynamics of a drug, therefore, the central effect (as the anticonvulsant response) and brain uptake of penbutolol given intravenously to mice with experimental inflammation have been measured. A significant decrease of the central effect of penbutolol and its brain uptake was seen in diseased when compared with control animals (P < 0.01). A parallel decrease in free fraction of penbutolol in diseased vs normal animals was detected. These results suggest that there is an increase in serum binding of basic drugs related to increments in α1‐AGP concentration, which reduces their central pharmacological effect. 1990 Royal Pharmaceutical Society of Great Britain