The effects of age on the pharmacokinetics, antihypertensive efficacy and general tolerability of dilevalol

Abstract

1. This study investigated the influence of age on the pharmacokinetics, pharmacodynamics, general tolerability and concentration-effect relationships in 18 patients with essential hypertension (age range 23-73 years) during treatment with dilevalol, a non selective beta-adrenoceptor antagonist with vasodilator properties. 2. There were no significant age-related changes in pharmacokinetics for either acute or chronic treatment with dilevalol, although there were significant changes in elimination half-life from 7.8 to 11.7 h (P less than 0.05) and in AUC from 261 to 352 ng ml-1 h (P less than 0.005) following translation from acute to chronic dosing. 3. In absolute terms, dilevalol treatment (as compared with placebo) produced numerically larger falls in average blood pressure in the six oldest as compared with the six youngest patients: for example, supine blood pressure fell by, respectively, 29/15 and 10/7 mm Hg during chronic treatment. 4. Using an integrated kinetic-dynamic model, blood pressure responsiveness was characterised by relating the fall in blood pressure (mmHg) to the plasma drug concentrations in each individual patient. No independent age-related effect was demonstrated. There was a significant relationship between response and the height of initial blood pressure which tended to be higher in the elderly patients. 5. Patient tolerability was generally satisfactory and there was no differential age-related effect. 6. This study has shown that the antihypertensive efficacy of dilevalol is not attenuated in the elderly and that there are no significant age-related differences in pharmacokinetics or pharmacodynamics.