Dose-response related efficacy in orthostatic hypotension of a fixed combination of D-camphor and an extract from fresh crataegus berries and the contribution of the single components.

Independent, double-blinded, randomized, placebo-controlled studies using sublingual/oral administration of D-camphor, an extract from fresh crataegus berries, and a combination of the two (CCC) yielded the following results: Both the D-camphor and the extract from fresh crataegus berries, the components of CCC, contribute to the pressoric effects of the combination. The underlying hemodynamic mechanisms can be attributed to an increase in total peripheral resistance induced by an increased tone of the arterioles with both components and the effect of crataegus is intensified by an additional direct positive action on cardiac performance. Conceivably, the D-camphor component is the main factor in inducing the rapid initial effect, whereas the extract from fresh crataegus berries adds a long-lasting effect.

Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension.

In order to test the efficacy of a combination of natural D-camphor and an extract of fresh crataegus berries (Korodin Herz-Kreislauf-Tropfen) on orthostatic hypotension, two similar, controlled, randomized studies were carried out in a balanced crossover design in 24 patients each with orthostatic dysregulation. The camphor-crataegus berry combination (CCC) was orally administered as a single regimen in 3 different dosages of 5 drops, 20 drops and 80 drops; a placebo with 20 drops of a 60% alcoholic solution served as control. Orthostatic hypotension was assessed with the tilt table test before and after medication.

Pharmacodynamic studies on the angiotensin II type 1 antagonists irbesartan and candesartan based on angiotensin II dose response in humans.

The in vivo effects of two unsurmountable angiotensin II type 1 (AT1) antagonists, irbesartan (150 mg) and candesartan (8 mg), were studied in a double-blind, randomized, crossover study in 18 healthy men. The drugs' direct vascular effects were assessed as the rightward shift (dose ratio - 1) of angiotensin dose-effect curves on diastolic blood pressure (DBP). Renal and adrenal effects were assessed by plasma renin activity (PRA), aldosterone concentrations, and antagonistic concentration equivalents (n x Ki) in a radioligand rat lung receptor assay.

Pharmacological differences among angiotensin II receptor antagonists.

Angiotensin II AT1 receptor antagonists (AIIRAs) have demonstrated efficacy similar to other classes of antihypertensive agents as well as "placebo-level" tolerability at all doses. Pharmacokinetic and pharmacodynamic studies provide a framework for understanding important intra-class dissimilarities. Disparity in antagonistic effects may be determined by in vivo responses to challenges of exogenous angiotensin II (Ang II) and by ex vivo/in vitro responses to a drug's biological activity by radioligand receptor assay (RRA).

Comparative pharmacodynamics and pharmacokinetics of candesartan and losartan in man.

The angiotensin II antagonistic effects of candesartan and losartan were compared in-vivo after single and repeated doses. Effects were related to antagonistic activity in plasma. In this double-blind, crossover study, 12 healthy male volunteers received, in random order, daily oral doses of 8 mg candesartan cilexetil or 50 mg losartan for seven days.

Time course and extent of angiotensin II antagonism after irbesartan, losartan, and valsartan in humans assessed by angiotensin II dose response and radioligand receptor assay.

Objectives: To compare the angiotensin II antagonistic properties of the usual recommended oral starting doses of various angiotensin II receptor antagonists-150 mg irbesartan, 80 mg valsartan, and 50 mg losartan-in humans.

Subjects And Methods: Eighteen healthy men were enrolled in a double-blind, randomized crossover study. Angiotensin II dose-effect curves of diastolic blood pressure and radioreceptor assay were performed before and up to 47 hours after single and multiple doses of the antagonists.

Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data.

Thioctic acid (TA), a racemate of R-(+)- and S-(-)-enantiomers of alpha-lipoic acid, acts as a powerful lipophilic, free-radical scavenger and is used in the treatment of diabetic neuropathy. This trial investigated the dose-linearity of enantiomer pharmacokinetics following the oral administration of single doses of 50 to 600 mg TA (formulation provided by ASTA (Medica)) in healthy volunteers. TA enantiomer concentrations in individual and pooled plasma samples were determined using enantioselective, high-performance liquid chromatography.

Blood pressure and aortic elastic properties--verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy.

The effects of 2 fixed antihypertensive combination drugs on blood pressure and aortic elastic properties were compared in 2 parallel groups. Twenty-six patients for 6 months received a calcium antagonist plus ACE inhibitor (verapamil SR 180 mg/trandolapril 1 mg (Vera/Tran)) and 25 patients a beta-adrenoceptor antagonist plus diuretic (metoprolol 100 mg/hydrochlorothiazide 12.5 mg (Meto/HCTZ)).

Angiotensin II antagonism and plasma radioreceptor-kinetics of candesartan in man.

Aims: The pharmacodynamic properties of the angiotensin II antagonist candesartan in humans were assessed from the rightward shifts of angiotensin II dose-effect curves (Schild regression technique). The pharmacokinetic characteristics were determined by radioreceptor assay (r.r.

Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction.

Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers were given a) a single 30 mg i.

Dose-effect and kinetic-dynamic relationships of the beta-adrenoceptor blocking properties of various doses of talinolol in healthy humans.

Twelve healthy subjects were investigated on six separate occasions at least 1 week apart when they either received a single oral dose of 80 mg propranolol; 25, 50, 100, or 400 mg talinolol; or placebo (double-blinded, period-balanced six-way cross-over design). The subjects were investigated during supine rest and performed supine bicycle ergometry 0200, 0500, 0730, 1000, and 2400 h after dosing. Isoprenaline (ISO) and epinephrine (EPI) were infused intravenously (i.

Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction.

Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers were given a) a single 30 mg i.

Agreement and reproducibility of the estimates of cardiovascular function by impedance cardiography and M-mode echocardiography in healthy subjects.

The reproducibility and agreement of the estimates of stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) by transthoracic impedance cardiography (ZCG) and M-mode echocardiography (ECHO) were analyzed before and after the placebo-controlled administration of ascending doses of isosorbide dinitrate and nicorandil in 12 healthy subjects. There was no biostatistical agreement between the two methods in estimating cardiovascular function either before or after dosing (ZCG estimated substantially larger SV, CO and lower TPR). But, ZCG and ECHO estimated about similar overall treatment related changes (across treatments and periods) and reached substantially better agreement when the values were expressed as ratio of the baseline before dosing.

Captopril does not interact with the pharmacodynamics and pharmacokinetics of digitoxin in healthy man.

The chronic oral administration of 0.07 mg digitoxin o.d.

Non-invasive assessments of compliance of the aortic wind-kessel in man derived from pulse pressure/storage volume ratio and from pulse wave velocity.

Two noninvasive methods for assessment of the compliance (1/E') of the aortic windkessel in man are presented and were tested for their ability to detect increases in stiffness of the aorta induced by atropine (0.012 and 0.024 mg/kg sequentially) in the presence and absence of a beta-blockade with propranolol 240 mg (n = 9).

Low frequency arterial wall movements for indirect blood pressure measurement in man. Validation of a method for non-invasive assessment of blood pressure under the influence of isoprenaline and angiotensin.

In order to measure blood pressure noninvasively, the second derivative of the low frequency wall movements of the brachial artery were registered with a piezo-electric pressure probe during deflation of a Riva-Rocci cuff along with the actual cuff pressure. Two characteristic phenomena of this signal have been suggested to reflect systolic and diastolic blood pressure. Appearance of a positive spike phenomenon (S) was suggested to indicate systolic blood pressure and disappearance of a negative preanacrotic notch (D) to indicate diastolic blood pressure.

The effects of oral enoximone on cardiac performance, calf arterial blood flow, and constrictor effects of norepinephrine infused into hand veins in humans.

Cardiac and peripheral vascular effects of enoximone were investigated in a placebo-controlled, crossover, double-blind trial in 10 healthy volunteers. Electromechanical systole (QS2c) revealed direct positive inotropic effects and venous occlusion plethysmography of the calf arterial blood flow before and 1, 2, 3, and 4 h following 3 mg/kg of enoximone orally. Norepinephrine (7-640 ng/min) dose-response curves of a superficial human hand vein were measured and enoximone and enoximone sulfoxide plasma concentrations determined at the same time points.

Antihypertensive treatment with cilazapril. Resting and exercise blood pressure, hormones and enzymes.

The effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril (Ro 31-2848) on resting and exercise blood pressure (BP) as well as on hormonal and enzyme activities were evaluated following a more than one year long-term treatment. After an initial placebo wash-out (mean sitting BP 151/101), n = 13 hypertensive patients were on cilazapril treatment (1.25, 2.

Does the combination of cilazapril and propranolol lower blood pressure at rest and during exercise more pronouncedly than either of the two components given alone?

The efficacy of three antihypertensive treatments given for 3 weeks each, 2.5 mg cilazapril, a new potent long-acting angiotensin-converting enzyme (ACE) inhibitor, 120 mg propranolol, and the combination of both, were compared in 17 patients suffering from essential hypertension. Blood pressure control (i.

Influence of the angiotensin converting enzyme inhibitor cilazapril, the beta-blocker propranolol and their combination on haemodynamics in hypertension.

This study compared the antihypertensive effects and the haemodynamic mechanisms of action of an angiotensin converting enzyme (ACE) inhibitor, a beta-blocker and the combination of both in patients with mild to severe hypertension. After a placebo run-in period of 2 weeks, patients were treated for 3 weeks with each of the following: cilazapril (2.5 mg daily) and propranolol (120 mg daily), in a randomized sequence, and thereafter a combination of the two drugs.