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Rom J Intern Med. 2011;49(1):75-84.

Comparing different treatment schedules of Zomen (zofenopril).

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"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.



Chronotherapy of hypertension became, during the last years, a main target in optimal BP values control, during 24 hours. Many clinical studies have demonstrated a different effect on blood pressure of the majority of angiotensin-converting enzyme inhibitors (ACEIs), studied as function of the moment of their administration. Until now, the majority of clinical proofs sustain the greater benefit offered by bedtime administration of ACEIs, concerning especially a significantly greater efficacy in reducing BP during the asleep period, thus increasing the prevalence of "dippers", the circadian profile considered to offer the best cardio-vascular prognosis, compared to at awakening administration.


This study investigated time-dependent effects of zofenopril (Zomen, 30 mg, Berlin-Chemie, Menarini Group, Romania) administration on ambulatory blood pressure values. We studied 33 consecutive untreated hypertensive patients (19 men, 14 women), 56 +/- 12.7 years old, with grade 1 or 2 uncomplicated essential hypertension (according to the European Society of Hypertension-European Society of Cardiology guidelines) (diagnostic formulated by casual determination and confirmed by an ABPM session at baseline), using zofenopril as monotherapy. The drug was initially administered in a single dose, at bedtime, during one month; after that period, we performed for all of them a new ABPM session, and, after that, for another month we administered the same drug, in single dose, at awakening. Blood pressure was measured for 48 hours before and after one month of treatment.


The blood pressure reduction during diurnal activity was similar for both treatment schedules. Bedtime administration of zofenopril, however, was significantly more efficient than at awakening administration in reducing asleep blood pressure. The awake:asleep blood pressure ratio was decreased after zofenopril on awakening but significantly increased towards a more dipping pattern, (from 60.60% to 90.90%) after at bedtime administration. The proportion of patients with controlled ambulatory BP increased from 51.51% to 84.84% (p < 0.001) by bedtime administration.


Nocturnal blood pressure regulation is significantly better achieved at bedtime as compared with at awakening administration of zofenopril, without any loss in efficacy during diurnal active hours; this might be clinically important, because nighttime blood pressure has been shown to be a more relevant marker of cardiovascular risks than diurnal mean values. The change in the dose-response curve, the increased proportion of controlled patients, and improved efficacy on nighttime BP values by bedtime administration of zofenopril should be taken into account when prescribing this ACEI for treatment of essential hypertension.

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