Objective—To compare the pharmacokinetic properties and bioavailability following oral and IV administration of bisoprolol, a second-generation β1-adrenoceptor–selective blocking agent, with those of carvedilol, a third-generation β1/β2 and α1-adrenoceptor blocking agent, in dogs.
Animals—12 healthy adult Beagles.
Procedures—A prospective, parallel group study was performed. The dogs were allocated to 1 of 2 groups (6 dogs/group) and were administered orally a 1 mg/kg dose of either bisoprolol or carvedilol. Following a 1-week washout period, each cohort received a 1 mg/kg dose of the same drug IV. Blood samples were collected before and after drug administration, and serum concentrations, pharmacokinetic variables, and bioavailability for each agent were assessed.
Results—After oral administration of bisoprolol, the geometric mean value of the area under the concentration-time curve extrapolated to infinity (AUCinf) was 2,195 μg/L (coefficient of variation [CV], 15%). After IV administration of bisoprolol, the dose-normalized geometric mean AUCinf was 2,402 μg/L (CV, 19%). Oral bioavailability of bisoprolol was 91.4%. After oral administration of carvedilol, the geometric mean AUCinf was 70 μg/L (CV, 81%). After IV administration of carvedilol, the geometric mean AUCinf was 491 μg/L (CV, 23%). Oral bioavailability of carvedilol was 14.3%. Total body clearance was low (0.42 L/h/kg) for bisoprolol and high (2.0 L/h/kg) for carvedilol.
Conclusions and Clinical Relevance—After oral administration, carvedilol underwent extensive first-pass metabolism and had limited bioavailability; bisoprolol had less first-pass effect and higher bioavailability. Collectively, these differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol.