The pharmacokinetics of two beta adrenoceptor blocking drugs, exaprolol and propranolol, in rats with interrupted enterohepatic circulation was studied. The tritium-labelled drugs were given intravenously to four groups of rats: control, bile-duct cannulated, bile-duct ligated, and pretreated with neomycin. Plasma levels and excretion were observed up to 96 h after administration. The pharmacokinetic parameters show an enhanced plasma elimination of both drugs at interrupted enterohepatic circulation compared to the control group. Significant changes were observed in the excretion pattern with bile-duct cannulated and bile-duct ligated rats, while the total radioactivity excreted in urine and faeces does not differ between control and neomycin pretreated rats.

The absorption rate of the beta-adrenoceptor blocking drug, exaprolol, from the gastrointestinal tract was studied using in-situ methods in the rat and dog. Exaprolol was rapidly absorbed from the small and large intestine of rats and from the ileum of dogs. The cardiac output and regional blood flow decreased in rats to approximately one half of the original values within 30 min of the in-situ experiment. The logarithm of the amount vs time plots from dogs were linear, whereas with rats a curvilinearity appeared apparently because of the blood flow-limited absorption kinetics of this highly lipophilic drug. The data obtained suggest that exaprolol is suitable for administration in sustained release form.