Comparison of a slow release formulation of oxprenolol with conventional oxprenolol in the treatment of hypertension.

Patients with moderate to severe hypertension were studied during a 12-week period, during which they were given a slow release formulation of oxprenolol once daily, in a dosage equal to their previous total daily dose of oxprenolol given in divided doses. There were no systematic differences between blood pressures at the beginning and end of the 12-week period. The once-daily dosage was well tolerated and was preferred by the patients. This regime offers advantages in terms of patient compliance with lifelong therapy in what is usually a symptomless condition.     

A comparison of slow release oxprenolol with conventional oxprenolol in the treatment of hypertension

Summary Sixteen patients with uncomplicated hypertension were studied in a double-blind within-patient trial comparing slow release oxprenolol (SRO) with conventional oxprenolol (CO). The antihypertensive effect of SRO once daily was greater than that of CO once daily, although this did not reach statistical significance. CO once daily was less effective than CObd and this difference was statistically significant for lying diastolic blood pressure. After exercise testing 26 hours post-dose, blood pressure and pulse rate were marginally lower on SRO than on CO, but this difference was not significant. Blood pressure readings 24 h post-dose were lower following morning dosing than following evening dosing, although pulse rates showed the opposite trend.     

Antihypertensive effect of diacetolol in essential hypertension.

1 Diacetolol is the N-acetylated metabolite of acebutolol and possesses beta-adrenergic receptor blocking properties. 2 Its antihypertensive action was assessed in accordance with a double-blind randomised cross-over scheme in 17 patients with moderate essential hypertension previously well controlled with acebutolol. 3 Significant reductions in lying mean arterial blood pressure were observed with daily doses of 200 mg (- 9%), 400 mg (- 10%) and 800 mg (- 14%), and were associated with significant decreases in heart rate and plasma renin activity. 4 The diacetolol mean plasma level measured 8 to 10 h after drug ingestion was proportional to the dose (207 +/- 27, 394 +/- 63 and 823 +/- 135 ng/ml for respectively 200, 400 and 800 mg/day).     

Comparison of the beta-adrenoceptor blocking activity of oxprenolol, slow release oxprenolol and a combined oxprenolol diuretic preparation.

1 Observations were made in five healthy subjects who exercised before and 2, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg slow release oxprenolol with 0.25 mg cyclopenthiazide and placebo. Blood samples were obtained before and at 1, 2, 3, 6, 8, 12 and 24 h after drug administration and assayed for oxprenolol concentration. 2 The three formulations produced maximum reductions of 29% in the exercise tachycardia 3 to 6 h after drug administration. At 24 h the effects of the three preparations were not significantly different from placebo. 3 There were no significant differences in the plasma concentrations produced by the three formulations during the 24 h period. 4 These observations suggest that the slow release formulations of oxprenolol should be given twice daily to maintain cardiac beta-adrenoceptor blockade throughout a period of 24 h.     

Trial of slow release diltiazem for essential hypertension in general practice

In New Zealand diltiazem has been approved since 1984 for the treatment of angina pectoris and was available only as short acting tablets. This study was a trial of a slow release formulation in the treatment of hypertension. A single blind placebo controlled study was undertaken on 24 patients in general practice using a once daily dose with a maximum of 360 mg. The mean fall in resting supine diastolic blood pressure was 17.3 mmHg, 95% CI 14.4 to 20.2; t = 12.2, df = 23, p = 0.0001. Twelve patients (50%) achieved a fall in diastolic pressure to 90 mmHg or less with the minimum dose (120 mg) while 19 patients (79%) achieved this level with up to 360 mg daily and 22 patients (92%) had a fall of diastolic pressure of 10 mmHg or more. One patient was withdrawn because of a rash. Other adverse reactions were mild and usually tolerable.     

Management of essential hypertension with oxprenolol and chlorthalidone in a fixed combination

A study was carried out in 40 patients with mild to moderate essential hypertension. The treatment administered was a fixed drug combination of oxprenolol (160 mg) and chlorthalidone (20 mg) in a single morning dose for 16 weeks. As a result, resting and standing blood pressure decreased significantly) (p less than 0.001). As regards clinical tolerance, this was adequate although treatment had to be discontinued in three patients. The minor side effects observed in other patients did not necessitate withdrawal of therapy. Only minor changes of the biochemical parameters were observed. It may be concluded that some patients with mild to moderate hypertension can be adequately treated with a single daily dose of a fixed drug combination of oxprenolol and chlorthalidone.     

尼卡地平缓释胶囊治疗原发性高血压62例

尼卡地平缓释胶囊治疗原发性高血压62例(男性38例,女性24例;年龄58±5a),其中51例单用尼卡地平缓释胶囊40mg, po, bid,共8wk;11例在原用卡托普利基础上加用该药,剂量方法同前。结果:显效45％(28/62),总有效率85％。该药对各种程度的高血压病患者疗效均较好,收缩压下降幅度达3.7±0.3kPa,不良反应小。     

Effect of slow release nifedipine tablets in patients with essential hypertension.

The antihypertensive effect of slow release nifedipine (CAS 21829-25-4) tablets (20 mg, Adalat) administered once or twice daily was studied in patients with essential hypertension of WHO stage I or II. Ambulatory blood pressure was monitored by a finger volume oscillometric device every 5 min for 24 h before and during the treatment with nifedipine. Whether administered once or twice daily, nifedipine tablets dit not change the pattern of circadian blood pressure variation; i.e. diurnal rise and nocturnal fall. Twice daily administration induced a significant downward shift in the blood pressure pattern. In other words, further hypotensive effect was observed during the night when the blood pressure was already low. On the other hand, administration once daily in the morning lowered daytime blood pressure without affecting blood pressure during the night. The duration of action of nifedipine tablets administered once daily was 12 h or more. In the acute experiment using 20 mg tablets of nifedipine, plasma concentration of nifedipine was well correlated with the percentage change in mean blood pressure. The minimal effective plasma concentration of nifedipine was estimated to be 13.4 ng/ml. However, in chronic treatment, nifedipine lowered blood pressure at the plasma concentration of 10 ng/ml. The results indicate that nifedipine tablets administered once daily provide an effective antihypertensive regimen for controlling daytime hypertension with minimal antihypertensive effect during the night.     

Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension

Summary The magnitude and duration of the antihypertensive effect of nifedipine were studied in 7 cases of moderate essential hypertension. In a double-blind crossover study, nifedipine 10 mg or a placebo were administered sublingually 4 times a day for 2 days, and the results were compared. Each dose of nifedipine reduced systolic and diastolic blood pressure by 14% both in the supine and upright positions. The antihypertensive action lasted for about 3 h and it was not cumulative. The reduction in blood pressure was associated with a temporary increase in heart rate. Administration of nifedipine 10 mg did not significantly raise plasma renin activity or plasma aldosterone. The drug was well tolerated and no side effects were detected.     

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.     

Antihypertensive effects of a new sustained-release formulation of nifedipine

The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week, double-blind, placebo-controlled study. Twenty-nine patients with mild essential hypertension were randomized to receive placebo (N = 9), 30 mg nifedipine (N = 10), or 60 mg nifedipine (N = 10). During treatment, 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 +/- 8/2 mm Hg and 141/98 +/- 15/2 mm Hg at baseline, respectively, to 126/89 +/- 9/7 mm Hg and 126/86 +/- 6/7 mm Hg (P less than .005). Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant (P less than .10) reduction in the mean 24-hour blood pressure of 2/6 +/- 8/8 mm Hg and 5/6 +/- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily, respectively. Diastolic blood pressure load (the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg) during 24 hours was decreased by 41% and 35%, with 30 mg and 60 mg nifedipine administered once daily, respectively. No significant dose response to nifedipine at these dose levels was observed. Although the once-daily formulation of nifedipine achieved effective control of office blood pressure, similar control was not observed in awake and 24-hour periods in all patients.     

Antihypertensive effect of atenolol alone or combined with chlorthalidone in patients with essential hypertension

1 The effect of atenolol, a cardioselective β-adrenoceptor acting drug, was studied alone or combined with chlorthalidone on blood pressure, heart rate, systolic time intervals, limb blood flow and limb vascular resistance. Plasma renin activity and plasma atenolol levels were also measured in the study.

2 Supine blood pressure was reduced in group A (11 patients) from 169.4 ± 5.06/111.2 ± 2.63 mmHg to 136.9 ± 2.55/90.9 ± 1.19 mmHg (P < 0.001) during the administration of atenolol alone. Concomitantly supine heart rate was decreased from 83.9 ± 4.10 beats/min to 59.7 ± 1.67 beats/min (P < 0.01) — 4th week. After the administration of atenolol over 8 weeks, supine blood pressure was 138.6 ± 1.21/94.4 ± 2.12 mmHg and supine heart rate was 59.5 ± 2.05 beats/min.

3 Supine blood pressure was reduced in group B (27 patients) from 183.6 ± 4.58/118.7 ± 2.01 mmHg (mean ± s.e. mean of systolic and diastolic blood pressure) to 171.3 ± 4.08/108.9 ± 2.26 mmHg (P < 0.01) during the administration of atenolol alone. Concomitantly supine heart rate was decreased from 84.0 ± 1.89 to 68.7 ± 1.94 (P < 0.001) beats/min. When atenolol was combined with chlorthalidone, supine blood pressure was reduced from 171.3 ± 4.08/108.9 ± 2.26 mmHg to 143.5 ± 3.68/94.8 ± 2.63 mmHg (P < 0.001). Heart rate did not alter significantly with the addition of chlorthalidone.

4 After the administration of atenolol alone in 12 patients of group B, there was a decrease of mean blood pressure from 131.8 ± 2.88 (mean ± s.e. mean) mmHg to 119.0 ± 4.05 mmHg (P < 0.001); of heart rate from 76.4 ± 3.58 beats/min to 57.0 ± 2.55 beats/min (P < 0.001); of calf blood flow from 9.23 ± 1.39 ml 100 g^-1 min^-1 to 5.05 ± 0.89 ml 100 g^-1 min^-1 (P < 0.001); and an increase of calf vascular resistance from 16.54 ± 1.90 (mmHg min^-1 100 g^-1)/ml to 28.53 ± 3.40 (mmHg min^-1 100 g^-1)/ml (P < 0.005). Atenolol did not alter significantly pre-ejection period index (P < 0.1). In atenolol-treated patients upon addition of chlorthalidone, there was a further decrease of mean blood pressure from 119.0 ± 4.05 mmHg to 105.9 ± 4.12 mmHg (P < 0.001). There were no further significant alterations of heart rate, pre-ejection period index, calf blood flow, and calf vascular resistance (P> 0.01).

5 Atenolol decreased plasma renin activity from 4.69 ± 0.87 to 2.85 ± 0.68 ng ml^-1 h^-1 (P < 0.05), and chlorthalidone increased it from 2.85 ± 0.68 to 3.81 ± 0.98 ng ml^-1 h^-1 (P < 0.05). Plasma renin activity on atenolol plus chlorthalidone was not significantly different from that on placebo (P> 0.1).

6 There was a 7.8 fold-interindividual variability in the relationship between plasma atenolol concentrations and the atenolol dose upon administration of a single oral dose of 100 mg.

     

The effects of oxprenolol on ambulatory intra-arterial blood pressure in essential hypertension

Summary Continuous intra-arterial blood pressure recording using the Oxford technique has been used to study the antihypertensive effects of oxprenolol taken three times daily in fully ambulatory patients with essential hypertension, outside hospital. During the first 24 h of treatment there was a reduction in daytime heart rate and a small reduction in daytime blood pressure. After 10 weeks treatment there was a more substantial fall in daytime blood pressure from the hour of waking, but no effect on sleeping nighttime blood pressure or heart rate. Twenty-four hour variation, as assessed by the amplitude of a fitted regression curve, showed a reduction in heart rate but not blood pressure variation. In 4 patients restudied after 11 weeks treatment with oxprenolol (tid) and cyclopenthiazide at 9 a.m. there was some evidence of an antihypertensive effect occuring during both the daytime and nighttime.     

Comparison of the activity and plasma levels of oxprenolol,slow release oxprenolol,long acting propranolol and sotalol

Summary Observations were made in 5 healthy subjects who exercised before and 1, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg long acting propranolol and 400 mg sotalol. Blood samples were obtained before and at 1, 2, 3, 6, 8, 10 and 24 h after drug administration and assayed for drug concentration. Although the plasma concentration of oxprenolol after S. R. oxprenolol was significantly less at 1 and 2 h and significantly greater at 24 h than after conventional oxprenolol, there was little difference between the effects of the two drugs on an exercise tachycardia. The plasma level of propranolol and the reduction in an exercise tachycardia after L. A. propranolol increased slowly to reach a peak at 6 h and then declined gradually to 24 h. The maximum plasma concentration and effect after sotalol occurred at 3 h and then declined with an elimination half-life of 12.1 h. At 24 h the percentage reduction in an exercise tachycardia was 8.3±2.5 after oxprenolol, 10.0±2.3 after S. R. oxprenolol, 18.0±3.2 after L. A. propranolol and 14.7±3.4% after sotalol.     

Serum level monitoring of a new slow release theophylline formulation in patients with chronic lung disease.

1 Serum theophylline levels were performed in 26 patients with chronic lung disease receiving rapid release theophylline (125 mg 6 hourly) and 28 patients receiving slow release theophylline (250 mg 12 hourly) under steady state conditions. 2 For rapid release theophylline the mean +/- s.d. serum theophylline levels at 0 and 2 h were 41.0 +/- 21.7 and 52.3 +/- 20.9 mumol l-1 respectively and for slow release theophylline at 0, 4 and 6 h 43.7 +/- 25.5, 50.9 +/- 23.0 and 51.7 +/- 26.4 mumol l-1 respectively. 3 Serum theophylline monitoring with slow release theophylline was performed in 70 patients with chronic lung disease. The initial dose was 250 mg administered 12 hourly. 4 The mean +/- s.d. steady state serum theophylline level achieved was 76.0 +/- 18.8 mumol l-1 and the mean +/- s.d. dose to produce this level was 9.4 +/ 2.3 mg kg-1 day-1. There was no correlation between dosage and serum theophylline level. 5 Sixty percent of patients required a dosage change for stabilization (375 to 1000 mg/day). Seventeen patients reported unwanted effects (nausea or tremor), which either settled quickly or resolved with dosage reduction. 6 Serum theophylline levels were obtained at different dosages in 44 patients and 18 patients demonstrated dose-dependent kinetics. 7 An initial dose of 500 mg/day is recommended and dosage increments should not exceed 125 mg/day with monitoring by serum theophylline levels.     

Experience with a slow-release formulation of oxprenolol.

Fifteen hypertensive patients with well controlled blood pressure on antihypertensive regiments consisting of a diuretic (in all but one) and a thrice-daily regimen of oxprenolol, were switched to an equal total daily dose of slow-release oxprenolol given once daily. Other drugs were continued unchanged. Observations on blood pressure and heart rate during half-day tests (lying, standing and post-exercise) indicated a little loss of control of the blood pressure towards the end of the 24-hour period when the next daily dose was due. Ectopic beats associated with exertion were observed more frequently at the end of the 24-hour period. Maximum advantage would seem to be gained by giving slow-release oxprenolol as a twice daily regimen with two-thirds of the daily dose in the morning and one-third at night.     

Pinacidil,a new vasodilator: Pharmacokinetics and pharmacodynamics of a new retarded release tablet in essential hypertension

In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I-II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p less than 0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p less than 0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the change in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p less than 0.05); four patients complained of oedema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive effects of lofexidine in patients with essential hypertension.

1 Single oral doses of lofexidine, 0.1, 0.3, and 0.6 mg produced dose related decreases in supine and standing arterial pressure and heart rate in nineteen patients with essential hypertension. 2 A mean oral antihypertensive threshold dose of less than 0.1 mg was estimated. 3 Lofexidine decreased mean urinary noradrenaline excretion 28% and caused significant retention of sodium and water. 4 The most prominent side effects were sedation and orthostatic dizziness. 5 Lofexidine is pharmacologically similar to, but apparently less potent than clonidine as an antihypertensive agent.