The effects of age on the disposition and hemodynamic responses to the selective beta(1) adrenoceptor antagonist were examined in an integrated manner using a combined pharmacokinetic--pharmacodynamic (PKPD) modeling approach. Thirty subjects were studied to represent, as far as was possible an age continuum. Single doses of acebutolol (20 mg) and placebo were administered intravenously and blood was withdrawn and heart rate and blood pressure were measured at frequent intervals up to 10 h post dose. No significant effects of age on the disposition of acebutolol and its major acetylated metabolite were apparent. Acebutolol when compared with placebo produced significant changes in blood pressure and heart rate and application of PKPD modeling demonstrated a significant negative correlation between blood pressure responsiveness to acebutolol and age.
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