SINGLE-DOSE AND STEADY-STATE PHARMACOKINETICS AND PHARMACODYNAMICS OFTHE ACE-INHIBITOR IMIDAPRIL IN HYPERTENSIVE PATIENTS

Aims To investigate the pharmacokinetic profile of the ACE-inhibitor i midapril in 10 hypertensive patients after a first single dose (10 mg) and after 28 days therapy with imidapril 10 mg once daily. Methods C- max, t(max), t(1/2) and AUC of imidapril and imidaprilat were obtained . ACE-activity and arterial blood pressure during imidapril were corre cted by a preceding placebo-investigation. Results The AUC of imidapri l was 140 (43 s.d.) ng ml(-1) h after the first dose and 123 (34 s.d.) ng ml(-1) h at steady state. AUC of the active moiety imidaprilat ave raged 211 (101 s.d.) ng ml(-1) h after the first dose and 240 (55 s.d. ) ng ml(-1) at the steady state investigation. Maximal ACE-inhibition was 75% after the single dose as well as at steady state. ACE inhibiti on before drug intake at day 28 (i.e. trough) was 50% The (placebo-cor rected) maximal drop in diastolic blood pressure after imidapril was 2 2 mmHg after the first dose and 25 mmHg at steady state. Exploratory a nalysis of imidaprilat plasma concentration vs effect profiles suggest s a hyperbolic concentration effect relationship where data of the sin gle dose contribute to the ascending part of an E-max-curve, whereas t he plateau around E-max is maintained at steady state. Conclusions In this group of hypertensive patients, the pharmacokinetic profile and t he drop in ACE-activity as well as in blood pressure seen after a sing le dose of imidapril and at steady state were similar. The initial res ponse to a test dose might therefore predict the response during chron ic dosing.