Bevantolol disposition in patients with hepatic cirrhosis

Bevantolol is a new, cardioselective beta-receptor antagonist that undergoes extensive hepatic biotransformation. To evaluate changes in the disposition of bevantolol produced by liver disease, a single 200-mg oral dose of bevantolol was administered in ten patients who had hepatic cirrhosis and to ten age-matched controls. Cirrhotic patients had a greater plasma bevantolol half-life (6.9 +/- 4.0 hr, mean +/- SD) then did patients with normal liver function (2.8 +/- 1.1 hr, P less than .01), and they also had a longer duration of significant bevantolol-induced heart rate slowing (for 12 hours after oral dose in cirrhotics versus three hours for controls). On the other hand, the peak concentration after the oral dose and the magnitude of bradycardiac effect were similar for both groups. Plasma bevantolol half-life was more variable in cirrhotic patients than in controls. Some of this variability among cirrhotics was attributable to age, which was a significant determinant of bevantolol half-life in the cirrhotic (but not in the control) patient sample. These results indicate that hepatic cirrhosis alters the disposition of bevantolol and suggest that modifications in bevantolol dose should be considered when using this drug to treat patients with liver disease.