Abstract
The pharmacokinetic profile of an oral single dose of the new cardioselective beta-blocking agent, bisoprolol, was studied in patients with moderate and severe liver disease (Pugh group B and C, respectively) and normal subjects. In patients with liver disease a significant increase in the drug elimination half-life, mean residence time, area under the curve, and time to reach maximum plasma concentration (Tmax) was observed with a significant reduction in the oral clearance compared with the control population. There was significant positive correlation between the Pugh Score (an objective measurement of hepatic dysfunction) and the volume of distribution. The drug was well tolerated although a rise in blood urea and creatinine of over 50% was observed in 4 of 9 patients with severe liver disease. In conclusion, the delayed absorption in these patients results in lower plasma concentrations and indicates that dose adjustment is not necessary but it is recommended that the upper limit for the daily dose should be set at 10 mg; this also applies under chronic dosing of bisoprolol.