ENALAPRIL PHARMACOKINETICS AND ACE-INHIBITION, FOLLOWING SINGLE AND CHRONIC ORAL DOSING

Twelve normal volunteers were given 10 mg enalapril maleate by single and 2 weeks multiple dose administration, and blood samples were colle cted for the determination of enalaprilat concentration and angiotensi n converting enzyme (ACE) activity. The mean terminal elimination half -life following a single administration of 10 mg enalapril, was 27 hou rs. The inhibition of ACE activity paralleled enalaprilat concentratio ns following both single and multiple dosing and the time of maximum i nhibition of ACE activity was associated on both occasions with maximu m concentration of enalaprilat. E(max) modelling of enalaprilat concen tration and ACE activity gave comparable values of Emax for both metho ds of administration. An accumulation factor of 1.7 was calculated fro m the area under the concentration time curve (AUC) of enalaprilat wit hin a dosing interval at steady-state and the total AUC following sing le administration of enalapril. There were no significant differences between males and females in the accumulation factor, half-life and AU C(inf).