Effects of Aging and Liver Disease upon the Pharmacokinetics of Nipradilol

Abstract

Objective: The effects of aging and liver disease on the pharmacokinetics of nipradilol were studied after a single oral dose of 6mg.

Study participants: Nipradilol was administered to three groups of subjects: younger healthy volunteers with a mean age of 33.2 years (group I, n = 6), older subjects without hepatic dysfunction with a mean age of 55.5 years (group II, n = 6), and patients with histologically confirmed cirrhosis of the liver with a mean age of 55.4 years (group III, n = 8).

Results: When compared with younger subjects (group I), the older subjects (group II) had a significantly longer time to maximum concentration, a greater area under the plasma concentration-time curve (AUC), a greater bioavailability (F), and a greater 24-hour urinary excretion of nipradilol. There was also a tendency towards a longer half-life in group II compared with group I. Cirrhotic subjects (group III) showed the same differences relative to group I. In addition, F was significantly larger and the plasma clearance was significantly decreased in group III compared with group II. Nearly identical results were demonstrated for the pharmacokinetics of denitrated nipradilol, one of the major metabolites of the test drug. A significant correlation was demonstrated between the AUC of nipradilol and age when groups I and II were combined.

Conclusion: It was concluded that the pharmacokinetics of nipradilol may be altered with aging and hepatic dysfunction, and that changes in metabolism are likely to be a major factor.