Comparative single dose and steady-state pharmacokinetics of bevantolol in young and elderly subjects

Summary The pharmacokinetics of bevantolol were examined following single and repeated oral doses to young and elderly volunteers. Following administration of a single 200-mg bevantolol tablet mean maximum plasma bevantolol concentrations in young and elderly subjects were 1690 ng/ml and 1810 ng/ml, respectively. Maximum bevantolol concentrations occurred approximately 1.1 h postdose in both young and elderly subjects. There were no significant differences in mean steady state bevantolol concentrations on Day 14 between young and elderly subjects. However, disproportionate increases in C_max, and in AUC, but not in t_max values were observed between Days 1 and 14.On Days 1 and 14, most young and elderly subjects exhibited monoexponential decline in bevantolol plasma concentrations after absorption phase. In those subjects Day 14 elimination half-lives in young and elderly were 1.9 and 2.2 h, respectively. In subjects who exhibited biexponential decline in bevantolol, an age effect in elimination became apparent, on Day 14 elimination half-lives were 5.7 and 11.2 h in young and elderly subjects, respectively. Bevantolol Metabolite III concentrations were observed in plasma of some subjects during the first 6 h after dosing. At steady-state AUC (0-ldc) values for the metabolite were less than 2% those of bevantolol.Bevantolol plasma levels accumulate to a small extent with repeated 200 mg daily doses. This is probably due to the contribution of a late and more persistent terminal elimination phase that was discernable in only certain individuals.