Antihypertensive effects and pharmacokinetics of single and consecutive doses of cilazapril in hypertensive patients with normal or impaired renal function.
(49/98)
1. A 1.25 mg dose of cilazapril, a new angiotensin-converting enzyme (ACE) inhibitor, was administered orally to two groups of hypertensive patients, five with normal renal function (NRF) and seven with impaired renal function (IRF), once daily for 5 or 8 consecutive days. Blood pressure, heart rate and serum ACE activity were measured up to 24 h following the initial and the last dose. Plasma level profiles of cilazapril and its active diacid were also evaluated on the first and the last day of treatment. 2. Cilazapril induced significant falls in both systolic and diastolic blood pressures without increasing heart rate. The antihypertensive effect was evident within 1 h after drug administration and was sustained for up to 24 h, particularly after consecutive dosing. 3. Serum ACE activity was markedly suppressed over 24 h. The recovery of ACE activity was delayed in the IRF group when compared with the NRF group. 4. Plasma concentrations of the active diacid in the IRF group were higher than in the NRF group with significant differences in the peak concentrations and area under the plasma concentration-time curve (AUC). The plasma concentration profile for the parent drug was similar for both the NRF and IRF groups. 5. A significant inverse correlation was found between the creatinine clearance and the AUC for the diacid. 6. Cilazapril is a potent ACE inhibitor with a prolonged duration of antihypertensive effect and is a useful agent for controlling blood pressure in hypertensives either with NRF or IRF. In patients with severe renal impairment the dose of cilazapril should be reduced. (+info)
Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure.
(50/98)
1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double-blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/- 3/96 +/- 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/- 1.8% and 8.0 +/- 1.9%, and after 1 week of treatment 5.0 +/- 2.4% and 8.1 +/- 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
The influence of prostaglandin inhibition by indomethacin on blood pressure and renal function in hypertensive patients treated with cilazapril.
(51/98)
1. In a placebo-controlled double-blind cross-over study lasting 6 weeks, twenty patients with essential hypertension were treated with placebo for 2 weeks followed by oral cilazapril 2.5 mg once a day or oral indomethacin 50 mg twice daily for 2 weeks. Afterwards they received the combination of both drugs for a further 2 weeks. 2. Cilazapril significantly lowered systolic and diastolic blood pressure for a period of 24 h post administration. 3. Indomethacin significantly attenuated the antihypertensive activity of cilazapril. This was more pronounced in those patients who were treated for the initial 2 weeks with indomethacin plus placebo (and subsequently with cilazapril in addition) than in the subjects who first received cilazapril plus placebo and then the combination. 4. Correspondingly the decrease of plasma renin activity (PRA) and urinary prostaglandin excretion (PGE2) was more pronounced in those patients treated initially with indomethacin. 5. The effect of indomethacin on the antihypertensive effect of cilazapril appears to depend upon the sequence of drug administration. (+info)
The influence of cilazapril on indices of autonomic function in normotensives and hypertensives.
(52/98)
1. In two single dose studies, acute blood pressure reduction with cilazapril was not associated with any significant change in supine or erect heart rate in either normotensives or hypertensives. 2. To investigate the lack of reflex cardioacceleration, a series of autonomic function tests was undertaken when there was maximum ACE inhibition, maximum evidence of angiotensin II withdrawal and the lowest blood pressure. 3. There was no evidence that cilazapril had any significant impact on indices of sympathetic nervous activity or the integrity of baroreflex mechanisms. 4. The results for the bradycardic response to apnoeic facial immersion, suggested enhanced parasympathetic activity, consistent with the withdrawal of the vagolytic actions of angiotensin II. 5. These results suggest that the absence of a heart rate response to ACE inhibition is not related to a profound sympatho-inhibitory effect or an impairment of baroreflex function. While there is some evidence of enhanced cardiac parasympathetic tone it seems unlikely that this is the sole explanation for the lack of cardioacceleration. (+info)
Haemodynamic and hormonal effects of cilazapril in comparison with propranolol in healthy subjects and in hypertensive patients.
(53/98)
1. The purpose of the present studies was to compare the pharmacodynamic profile of the new ACE inhibitor cilazapril with the beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients. 2. Hormonal and haemodynamic responses at rest and after pharmacological interventions with angiotensin I and isoprenaline were investigated in six healthy volunteers following a 1 week treatment with placebo, propranolol (120 mg day-1) and cilazapril (2.5 mg day-1) in a double-blind cross over design with a wash-out period of 1 week between the different treatments. 3. Cilazapril induced a pronounced increase of plasma renin activity and angiotensin I concentrations, whereas after propranolol both parameters decreased. After both compounds slight decreases in angiotensin II concentrations were found. After the pharmacological challenges with angiotensin I and isoprenaline specific effects of the ACE inhibitor and beta-adrenoceptor blocker were found respectively. 4. Seventeen hypertensive patients received after a 2 week placebo period in random order cilazapril (2.5 mg day-1) or propranolol (120 mg day-1) for 3 weeks. A cross over design switched the patients to the other treatment. On the last day of each treatment period blood pressure, heart rate, cardiac output and total peripheral resistance were determined at rest and during handgrip test. In addition, bicycle exercise test was done and blood lactate concentrations were determined. 5. At rest blood pressure was lowered by both drugs, but total peripheral resistance increased after propranolol and decreased after cilazapril. After hand grip test, blood pressure was lowered after both drugs, but peripheral resistance decreased only after cilazapril.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Pharmacokinetic and pharmacodynamic interactions between the ACE inhibitor cilazapril and beta-adrenoceptor antagonist propranolol in healthy subjects and in hypertensive patients.
(54/98)
1. Six healthy subjects received cilazapril (2.5 mg once daily), propranolol (120 mg once daily), the combination of both and placebo for a period of 1 week each (wash-out phase 1 week). 2. Propranolol and cilazapril reduced systolic and diastolic blood pressure (BP) by 7 mm Hg at peak when compared with placebo. However after the combination, this reduction was more than doubled (18 mm Hg) and lasted longer. 3. There was a trend to lower and later peak concentrations for both drugs after administration of the combination. No clinically relevant pharmacokinetic interactions between cilazapril and propranolol were found. 4. The effects on blood pressure were confirmed in hypertensive patients (BP diastolic greater than 95 mm Hg). Thirteen patients were randomly allocated cilazapril (2.5 mg day-1) or propranolol (120 mg day-1] as part of a cross-over design. This was then followed by the combination. All treatment periods were of 3 weeks duration and all measurements were done 2 h after drug administration. 5. Cilazapril lowered the median sitting diastolic BP by 8 mm Hg, and propranolol by 9 mm Hg, whereas the combination reduced the diastolic BP by 19 mm Hg. 6. The results of these studies, attempting to elucidate drug-drug interactions, showed that combined use of propranolol and cilazapril resulted in a more pronounced and longer lasting blood pressure reduction, in healthy subjects and in patients with hypertension. (+info)
Pharmacokinetics and effects on renal function following cilazapril and hydrochlorothiazide alone and in combination in healthy subjects and hypertensive patients.
(55/98)
1. Possible interactions between cilazapril and hydrochlorothiazide with respect to pharmacokinetics and renal effects were investigated in healthy subjects (single dose) and in hypertensive patients (multiple dosing). 2. No significant pharmacokinetic interaction was found between cilazapril and hydrochlorothiazide. 3. Cilazapril showed weak saluretic properties as compared with hydrochlorothiazide, but increased the saluretic effects of hydrochlorothiazide. 4. Cilazapril attenuated the hypokalaemia observed with hydrochlorothiazide in hypertensive patients. 5. The effect on blood pressure reduction obtained from the combination of cilazapril and hydrochlorothiazide lasted longer than that of cilazapril alone. (+info)
Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.
(56/98)
Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II. (+info)