Comparison of the haemodynamic effects of bucindolol, propranolol and pindolol in healthy volunteers.

The effects of single oral doses of bucindolol (50, 100, 200 and 400 mg), pindolol (10 mg), propranolol (160 mg) and placebo on arterial pressure and heart rate in the supine and standing positions and exercise heart rate were compared in 12 healthy male volunteers. Supine heart rate was significantly greater after all four doses of bucindolol and pindolol in comparison to propranolol. Bucindolol had no significant effect on standing heart rate which was significantly reduced by pindolol and propranolol. Bucindolol, pindolol and propranolol significantly reduced an exercise tachycardia for at least 24 h after drug administration. Supine systolic pressure was not affected by any treatment but supine diastolic pressure was significantly reduced by bucindolol (200 and 400 mg) and by pindolol. All doses of bucindolol, propranolol and pindolol significantly reduced standing systolic blood pressure. There was a significant linear trend for reductions in standing systolic blood pressure and increasing doses of bucindolol. Standing diastolic blood pressure was significantly reduced by bucindolol 200 and 400 mg. Faintness and light headedness occurred in 6 of 12 subjects after 200 mg bucindolol and in 8 of 10 subjects after 400 bucindolol. After bucindolol, analysis of plasma samples demonstrated the presence of bucindolol, 5-hydroxy and 6-hydroxy bucindolol and indolyl-t-butylamine. These observations indicate that in man, bucindolol is a beta-adrenoceptor blocking drug with hypotensive activity and probably partial agonist activity. It is unlikely that the hypotensive effects result from blockade of beta-adrenoceptors or from the drug's partial agonist activity.     

A placebo controlled comparison of the effects of metoprolol and celiprolol on echo-Doppler measurements of cardiovascular function in normal volunteers.

1. This study used a continuous-wave echo-Doppler method (Exerdrop) to investigate the effects of beta-adrenoceptor antagonism and partial agonism on cardiovascular responses at rest and during dynamic exercise. 2. A double-blind, randomised, placebo controlled comparison of metoprolol (50 mg) and celiprolol (200 mg) was undertaken in nine normal volunteers; single oral doses of medication were administered at weekly intervals. Rest and exercise (supine bicycle) haemodynamics were assessed at 0, 2, 4, 6 and 8 h following dosing. 3. Before dosing and after placebo, the aortic flow velocity, acceleration and velocity integral increased progressively during exercise, as did heart rate, blood pressure and cardiac output. 4. Following metoprolol 50 mg, heart rate was significantly reduced without change in systolic or diastolic blood pressure. Echo-Doppler peak acceleration and velocity decreased at rest. On exercise, heart rate and systolic blood pressure fell significantly; the increase in acceleration was significantly blunted compared with placebo (a decrease of 15.2% at rest and 22.9% at 75 watts; P < 0.01 vs placebo). Peak velocity fell significantly by 75 watts exercise. 5. Celiprolol 200 mg at rest significantly increased systolic blood pressure, peak acceleration and velocity. On exercise celiprolol, in contrast to metoprolol, did not reduce peak acceleration or peak velocity; however exercise heart rate and systolic blood pressure were significantly reduced. The difference between celiprolol and metoprolol in respect of peak acceleration persisted over the 8 h of the study. 6. These differences between metoprolol and celiprolol are compatible with the partial agonism of celiprolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of two oxprenolol oral osmotic (OROS) delivery systems in patients with essential hypertension

Summary The effects of two oxprenolol oral osmotic (OROS) delivery systems on heart rate and blood pressure before and during recovery from exercise at a predetermined load were examined in twelve patients with hypertension previously responding to beta-blocker monotherapy. Haemodynamic responses were attenuated during the 24 h after single and repeated (15 days') once daily administrations of 10/170 and 16/260 oxprenolol OROS.At 24 h after repeated doses, compared to placebo there were significant reductions in resting blood pressure and in heart rate immediately following exercise. Attenuation of heart rate after exercise was dose related but differences between the systems with respect to resting heart rate and blood pressure were inconsistent. Antihypertensive responses after repeated doses were greater than those after single doses.However, reductions in resting and exercise heart rates were consistently less on chronic therapy. This may reflect enhanced expression of the partial agonist activity of oxprenolol due to altered receptor sensitivity after prolonged beta-blockade.The plasma oxprenolol profiles after both systems indicated slow absorption and substantial concentrations were apparent 24 h after drug administration.These observations suggest that both oxprenolol OROS systems display sustained drug release and on once daily dosing provide 24 h beta-blockade and control of blood pressure at rest and following exercise.     

Hemodynamic effects during rest and exercise of bucindolol in hypertensive men

Bucindolol is an investigational beta-adrenergic blocking agent with intrinsic sympathomimetic and vasodilatory activity in animals. In a double-blind, six-way, crossover study of six mild-to-moderate hypertensive men, the effects of bucindolol 100, 200, and 300 mg/d on resting blood pressure, heart rate, forearm blood flow, and vascular resistance measured by pneumoplethysmography, and blood pressure and heart rate after cycle and handgrip exercise were compared with those of propranolol 160 and 320 mg/d and placebo after q12h administration for five doses. Both bucindolol and propranolol significantly suppressed heart rate after cycle exercise in comparison with placebo (-33 to -48 beats/min), demonstrating beta blockade. Suppression of resting heart rate by propranolol (-20 beats/min) was significantly (P less than .05) greater than bucindolol (-7 to -8 beats/min); a similar treatment difference in heart rate was noted after handgrip exercise (-18 to -19 vs -1 to -8 beats/min, respectively). Bucindolol and propranolol decreased resting blood pressure to the same extent (in comparison with placebo; P less than .05 at peak activity, 2 hr postdose). Bucindolol tended to increase forearm blood flow and decrease forearm vascular resistance (P less than .05 at 4 hr postdose) in comparison with placebo. The effect of propranolol on forearm blood flow and forearm vascular resistance was not significant compared with placebo. These data are consistent with intrinsic sympathomimetic and vasodilatory activity of bucindolol in hypertensive men.     

A comparison of slow release with conventional oxprenolol: plasma concentrations and clinical effects.

1 Plasma concentrations of oxprenolol have been compared in six healthy volunteers after 80 and 160 mg doses of a new slow release (SR) oxprenolol preparation, after an 80 ng dose of conventional oxprenolol (CO), and after the second of two 80 mg doses of conventional oxprenolol given 12 h apart. Basal pulse rates and blood pressures, and pulse rates before and after a standard exercise test have been compared after the four active treatments and after a placebo. 2 Peak plasma concentrations of oxprenolol attained after 160 mg of the slow release preparation were similar to the peak concentrations after the single 80 mg dose of conventional oxprenolol. Higher concentrations, however, persisted for much longer after the slow release preparations than after the conventional preparations. 3 Neither oxprenolol formulation had any effect on resting pulse rate or blood pressure in normotensive volunteers. 4 Comparison with placebo showed that the single dose of the conventional oxprenolol produced a significant reduction in exercise induced tachycardia for 8 h whereas the high dose of the slow release preparation produced a similar reduction which lasted for at least 14 hours.     

Twenty-four hour effects of oxprenolol oros and atenolol on heart rate,blood pressure,exercise tolerance and perceived exertion

Summary The effects of oxprenolol, a non-selective beta-blocker with moderate intrinsic sympathomimetic activity (ISA), given by the Oros delivery system, on resting and exercise heart rate and blood pressure have been compared over a 24-h period with those of atenolol, a beta₁-selective blocker without ISA. The effects on maximal and submaximal exercise tolerance and perceived exertion were studied in relation to the level of beta-blockade. 9 healthy subjects were treated with placebo, atenolol, 100 mg/day and oxprenolol Oros, 16/260 mg/day in random order, each for 5 days. Progressive maximal exercise tests and submaximal endurance tests at 80% of maximum aerobic exercise capacity were performed 2, 5 and 24 h after intake of the drugs.The reduction of blood pressure 2 and 5 h after drug intake was less pronounced after oxprenolol Oros than after atenolol, but by 24 h after the last dose the effects were similar. The peak level of beta-blockade (i.e. reduction in maximal exercise heart rate) was similar after oxprenolol Oros and atenolol. The minimal level of beta-blockade 24 h after the last dose was greater after oxprenolol Oros than after atenolol. Maximal exercise capacity and submaximal exercise tolerance were impaired after both beta-blockers. The subjective feeling of exertion did not differ between placebo, atenolol and oxprenolol Oros when related to the relative work load, except after the first minute of exercise, when the rating of perceived exertion was higher after atenolol.     

Comparison of prizidilol hydrochloride (SK & F 92657), a new antihypertensive agent with beta-adrenoceptor antagonist and vasodilator activity with propranolol and hydralazine in normal volunteers.

1 Some cardiovascular pharmacology of prizidilol hydrochloride, a new antihypertensive compound with precapillary vasodilator and beta-adrenoceptor antagonist activity, in man is described. 2 To investigate further the pharmacological profile of this drug the effects of a single oral dose of 400 mg prizidilol hydrochloride were compared with propranolol 40 mg in combination with either 25 mg or 50 mg of hydralazine for up to 6 h after dosing, in a placebo controlled in eight healthy subjects. 3 Prizidolol hydrochloride significantly reduced supine and standing diastolic blood pressure and was more effective than propranolol combined with either dose of hydralazine in this respect. 4 Supine heart rate was significantly increased after prizidilol hydrochloride, but was not significantly changed after propranolol combined with either dose of hydralazine. The reasons for the increase in supine heart rate after prizidolol are discussed. 5 beta-adrenoceptor antagonism was assessed in terms of inhibition of exercise induced increases in heart rate and systolic blood pressure. At the doses used, prizidolol hydrochloride was less effective than propranolol and hydralazine combined, particularly during the first 3 h after dosing.     

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta-adrenoceptor blocking drug.

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10, 20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 +/- 2.2%) occurred after 40 mg. 3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3 +/- 2.7% reduction and a further decline to 48 h when there was a 14.6 +/- 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 +/- 2.5, 15.9 +/- 4.9 and 15.1 +/- 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent beta-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.     

Comparative effects of alinidine and propranolol in ischaemic heart disease

Summary The effects of single oral doses of alinidine 40 mg, propranolol 40 mg or placebo during a maximal exercise test on a bicycle ergometer in patients with angina pectoris were studied in a randomised, double blind study. 2 and 5 h after drug intake a small fall in resting heart rate and systolic blood pressure was observed both after alinidine and propranolol. At a fixed work load both drugs decreased heart rate, systolic blood pressure, double product and the extent of ST segment depression. Total work performed and time to appearance of angina pectoris were increased 2 h alinidine and propranolol. The same effects were still apparent 5 h after propranolol but not after alinidine. At peak exercise neither drug had any effect on the extent of ischaemic ST segment depression.     

Comparative effects of adimolol, labetalol and propranolol on heart rate and blood pressure in man.

The cardiovascular effects of adimolol, a new, potent, long acting beta-adrenoceptor blocking drug were investigated in three studies. In the first study blood pressure and heart rate were measured in five male volunteers before and at 2, 4, 6, 8, 24, 32, 48, 72 and 96 h after single oral doses of adimolol. All doses of adimolol reduced supine, standing and exercise heart rates in a dose dependent manner. The maximum effect ranged from 18% following 25 mg to 29% following 600 mg and all doses showed an effect at 96 h (range 3.5-17.2%). In the second study the effects of adimolol, 25 and 400 mg, labetalol, 200 and 800 mg, propranolol 40 mg and placebo were compared on supine and standing heart rate and blood pressure and on exercise heart rate before and at 2, 4, 6 and 8 h after single oral doses. The exercise heart rate was significantly reduced at all times following adimolol 25 and 400 mg, labetalol 800 mg and propranolol 40 mg. At 2 h all the drugs significantly reduced standing systolic blood pressure. In the third study, 4 h after single oral doses of adimolol 400 mg, labetalol 400 mg and propranolol 40 mg six subjects received serial 4 min infusions of phenylephrine. The blood pressure was measured after each infusion. Labetalol 400 mg significantly shifted the blood pressure dose-response curve to the right. There was no difference between propranolol 40 mg and adimolol 400 mg. These studies show that adimolol is a potent, long acting beta-adrenoceptor blocking drug without evidence of alpha-adrenoceptor blockade in man.     

Concentration-effect relationships for oxprenolol in patients with essential hypertension.

1. Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2. Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P less than 0.001), but differences were slight. 3. Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4. The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.     

Comparison of the duration of antihypertensive action of atenolol and metoprolol over a 24-hour period

The antihypertensive and beta-blocking effect of 100 mg atenolol and 100 mg metoprolol each given once daily were compared using an observer-blind, randomized, placebo-controlled crossover study. Blood pressure and heart rate were measured 22 hours after the last tablet of a 2-week dosing period. Twenty-five patients completed the study. Both drugs caused a significant decrease in supine and standing blood pressure, with atenolol effecting, numerically, the greater reductions. The decrease in standing diastolic blood pressure was significantly greater with atenolol than with metoprolol (p less than 0.05). Metoprolol at 22 hours post-dosing did not differ from placebo in the control of exercise systolic blood pressure (191.1 v 194.6 mmHg): the exercise systolic blood pressure achieved on atenolol (177.3 mmHg) was significantly lower than that achieved on both placebo (p less than 0.001) or metoprolol (p less than 0.05). The heart rates achieved on atenolol were significantly lower than those achieved on metoprolol in similar circumstances (p less than 0.001). It is concluded that, at the doses examined in this study, atenolol is the more suitable agent for the control of supine, standing and exercise blood pressure over 22 hours.     

Long acting beta-blockers in the twenty fourth hour

Fifteen mild to moderate hypertensives were submitted to exercise testing using a bicycle ergometer with a fixed load. Heart rate, blood pressure and ECG were recorded throughout 5 min exercise and 10 min recovery. Oxygen uptake was measured during the final minute of exercise and blood glucose estimation and serum drug levels assessed 5 min after recovery. The above measurements were made after exactly 24 h following seven days administration of 160 mg of long acting (L.A.) propranolol, 200 mg of sustained action (S.A.) metoprolol and two matched placebos. Propranolol L.A. was superior to Metoprolol S.A. in the reduction of exercise induced tachycardia and both drugs were significantly superior to placebos. Both drugs were effective agents for the lowering of resting blood pressure after 24 h but propranolol L.A. was more effective in the lowering of systolic peaks observed during exercise. There was no significant effect upon oxygen uptake and blood glucose. The incidence of side effects was low and showed no significant difference from placebo.     

Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers

The cardiovascular effects of single oral doses of nifedipine (20 mg), atenolol (50 mg), or of their combination were compared with placebo in a double-blind randomized cross-over study in 10 normotensive volunteers. After subjects rested for 2 h, before drug administration, heart rate, blood pressure, stroke volume index, and cardiac index were measured noninvasively. These cardiovascular parameters were then determined prior to and after exercise periods (160 W, 10 min, bicycle ergometry) which were performed 40, 70, 130, 190, 310 min, and 22 h after drug intake. Nifedipine decreased resting diastolic blood pressure (p less than or equal to 0.05) after 2 h, whereas systolic blood pressure remained unchanged and heart rate significantly increased at rest and after exercise. Stroke volume index and cardiac index were unaffected. Atenolol significantly decreased systolic and diastolic blood pressure as well as heart rate; stroke volume index following exercise increased significantly, and cardiac index was unchanged. Administration of the combination caused a significantly more pronounced fall of systolic and diastolic blood pressure as compared with either drug alone, whereas the negative chronotropic effect was not different from that of atenolol. As did atenolol, the combination increased stroke volume index after exercise with no change in cardiac index. Maximum plasma concentrations of nifedipine (37.1 +/- 16.7 ng/ml) and atenolol (276.3 +/- 107.2 ng/ml) and terminal half-life of atenolol (9.9 +/- 2.6 h) were not altered by combined administration of the drugs.     

Hypotensive effect of oxprenolol in mild to moderate hypertension: a multicentre controlled study

Summary In a multicentre, double-blind, between-patient study the hypotensive effect of oxprenolol was investigated in 329 patients with mild to moderate hypertension. A factorial experimental design with three factors was chosen: oxprenolol — none or daily doses of 20, 40, 60 and 80 mg; dihydralazine and hydrochlorothiazide, respectively, none or 30 mg daily. Each treatment was given for 4 weeks after an adequate period of withdrawal from any other possible hypotensive therapy and one week of placebo wash-out. Irrespective of the association with dihydralazine and/or hydrochlorothiazide, oxprenolol had a hypotensive effect linearly related to dose for standing systolic (P<0.05) and diastolic (P<0.01) pressure, and for lying diastolic (P<0.05) pressure. The addition of dihydralazine enhanced the time-course of the hypotensive effect of oxprenolol, particularly the 80 mg dose level. In general, the combination of oxprenolol with dihydralazine and hydrochlorothiazide caused larger reductions in blood pressure, particularly with oxprenolol 80 mg. In the latter group, the eventual falls in blood pressure were 30.5 and 14.4 mmHg for lying systolic and diastolic, respectively; and 32.1 and 20.0 mmHg for the standing systolic and diastolic pressures. The drug was well tolerated; major side effects (heart failure and bronchospasm) occurred in three patients.A brief communication on this study was presented at the Second Meeting of the International Society on Hypertension, Milan, Sept. 20 – 23, 1972     

The comparative beta-adrenoceptor blocking effects of penbutolol,atenolol and sustained-release metoprolol in healthy volunteers

Summary The effects of penbutolol (40 mg), atenolol (100 mg) and sustained-release metoprolol (metoprolol SA) (200 mg) upon heart rate (HR) and blood pressure (BP) at rest and during bicycle ergometer exercise, have been compared in 12 healthy young men using a double-blind crossover design. Measurements of each drug's effect were made before and at 3, 10 and 24 h after a single dose, and again at 24 h after the last of seven consecutive daily doses. Resting HR and systolic BP were reduced to an equivalent extent by all three drugs. During the third minute of exercise, the effects of penbutolol and atenolol upon HR and systolic BP were consistently similar and greater than those of metoprolol SA.     

The effects and dose-response relationship of xamoterol in patients with ischaemic heart disease.

1. In a double-blind placebo controlled four-way crossover study the effects and dose response relationships of xamoterol were studied in nine patients with angina and dyspnoea secondary to chronic left ventricular dysfunction. The duration of exercise on a treadmill and heart rate were measured at the end of each phase of the study at 2 h and 24 h after dosing. 2. Xamoterol at 200 mg and 400 mg orally once daily had no effect on the mean resting heart rate but there was a small (5.7 beats min-1) but significant reduction in resting heart rate on 600 mg at 2-2.5 h after dosing. All three doses of xamoterol significantly reduced the maximum exercise heart rate at 2-2.5 h after dosing. 3. Xamoterol at all three doses significantly increased exercise duration at 2-2.5 h after dosing but not at 24 h. 4. Mean plasma xamoterol concentration at both 2-2.5 h and 24 h after dosing were dose related. The EC50 for xamoterol is 33.5 ng ml-1, where EC50 is the effective plasma concentration required to produce 50% of the maximum effect on exercise heart rate.     

Cardiovascular effects of cromakalim (BRL 34915) in healthy volunteers.

1. The effect of oral doses of cromakalim 0.5, 1.0, 1.5 and 2.0 mg on several cardiovascular parameters was studied in healthy male volunteers. 2. In the first study, no dose of cromakalim reduced systolic or diastolic blood pressure in the supine or standing position. Reductions of diastolic blood pressure after exercise (P less than 0.01) were observed 4 h after administration of 2.0 mg. 3. There was a trend towards increased heart rate after 2.0 mg at all time intervals, and significant changes were observed in supine and standing heart rate at 2 and 4 h (P less than 0.01). No significant change was observed in exercise heart rate. 4. In the second study small increases in forearm blood flow were observed from 3 h to 5 h after oral administration of 1.0 and 2.0 mg of cromakalim. Forearm vascular resistance was significantly reduced after 2.0 mg (P less than 0.025) when compared with placebo. No change was observed in forearm venous capacitance after either dose of cromakalim, or placebo. Supine heart rate was significantly increased 4 h after 2.0 mg of cromakalim (P less than 0.025). 5. These results show that oral administration of cromakalim decreases diastolic blood pressure and forearm vascular resistance. A hypotensive effect is probably attenuated by reflex tachycardia.     

Pharmacodynamic and pharmacokinetic study of oral and intravenous penbutolol

The present study was done to establish the dose-response relationships for effects on heart rate and systolic and diastolic blood pressure, tolerance and plasma disappearance kinetics after large intravenous and oral doses of penbutolol. Twelve healthy volunteers were randomly allocated to receive penbutolol (n = 8) or placebo (n = 4) in this single blind, placebo-controlled investigation. The degree of beta-blockade was measured by standarized exercise tests at work loads selected to produce a heart rate of 150/min without treatment. Penbutolol was given as single i.v. doses of 3, 6 and 12 mg and as 40, 80 and 120 mg once daily for one week, measurements being made 2 and 24 h after the last dose. Penbutolol i.v. did not influence the resting heart rate but it did reduce resting systolic blood pressure in a non-dose dependent manner. Exercise heart rate and systolic pressure were lowered by all the intravenous doses. All oral doses of penbutolol lowered exercise heart rate and systolic blood pressure to the same extent. The reductions in exercise tachycardia was still present after 24 h. After i.v. administration t1/2 was approximately 1.2 h and the volume of distribution was 32-421. All doses were well tolerated.     

Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time

The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)