The disposition and metabolism of14C-oxprenolol·HCl in man
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1. The disposition and metabolism of oxprenolol have been investigated in two healthy male volunteers, following a single 160 mg oral dose of racemic 14C-labelled oxprenolol.2. Absorption was rapid and complete. Peak blood concentrations of total radioactivity were 8.83 and 8.21 nmol.g−1 after 1 and 1.5 h in the two subjects. After 4 days 93.4 and 81.90% of the dose was excreted in urine, and a total of 96.6 and 84.5% found in the excreta.3. Mean peak blood concentrations of unchanged R(+)—and S(—)—oxprenolol were 0.83 and 0.81 nmol.g−1. Maximal concentrations of the glucuronides of the R(+)—and S(—)—isomers were 1.98 and 3.51 nmol.g−1. The mean half-lives of both oxprenolol enantiomers were 1.8 h, those of their glucuronides were 3.2h (R(+)) and 4.6h (S(—)).4. Unchanged oxprenolol and the oxprenolol glucuronides constituted 11.4 and 66.5% of the area under the blood concentration-time curve (AUC, 0–24 h) of total radioactivity. The AUC-ratio of R(+) to S(—) was 1.19 for free oxprenolol and 0–36 for the glucuronides. Free metabolites II-X represented together 4.3% of 14C-AUC, and their glucuronides 15.2%.5. In urine, 1.8 and 1.0% of the total radioactivity was present as unchanged R(+)—and S(—)—oxprenolol, respectively. The glucuronides of the enantiomers accounted for 24.5 and 26.5%. The percentages of free 4- and 5- hydroxy oxprenolol were 0.7 and 2.4% while those of their glucuronides were 12.3 and 7.5%. Metabolites IV-X constituted together 6.2% in free form and 5.3% in conjugated form.6. In conclusion, the good mass balances in blood and urine has enabled the comprehensive and quantitative description of the metabolic fate of oxprenolol in man. Oxprenolol is extensively metabolized, direct O-glucuronidation being the major metabolic pathway and oxidative reactions minor ones. The disposition of the oxprenolol enantiomers revealed no remarkable stereoselective differences.Keywords:
Oxprenolol
Oxprenolol
Pindolol
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Oxprenolol, a new beta adrenergic blocking drug, was used as the sole antihypertensive agent for a minimum of 14 weeks in 20 patients with mild to moderate essential hypertension. The results demonstrate a definite, but not prominent, antihypertensive activity of this drug. Oxprenolol does not lower the blood pressure sufficiently in an unselected group of patients, but its effect is clinically satisfactory and well tolerated in some cases of mild “borderline” hypertension. In the latter, low doses of oxprenolol influence equally the systolic and diastolic blood pressure in both supine and standing position. The decrease in heart rate is relatively small. No maior side effects were noted.
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Essential hypertension
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1. The use of large doses of oxprenolol and a diuretic had a stronger antihypertensive action than the diuretic alone. 2. The combined use of oxprenolol and a diuretic had a strong antihypertensive effect in a majority of the mild, moderate and severe hypertensive patients studied. 3. Oxprenolol caused strikingly few side effects, and it especially did not cause cardiac insufficiency when used in combination with a diuretic. 4. When dihydralazine was added to oxprenolol, it did not cause a further significant fall in arterial pressure, except in a few impressive instances.
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1. Patients with moderate to severe hypertension were studied during a 12 weeks period, while taking a slow-release formulation of oxprenolol once daily, in a dose equal to their previous total daily dose of oxprenolol given in divided doses. 2. There were no significant differences between blood pressure at the beginning and end of the 12 weeks period. 3. Once-daily dosage offers advantages of patient compliance.
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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.
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Racemic mixture
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In controlled trials of the beta-adrenergic blocking drugs oxprenolol and practolol in hypertension both drugs were well tolerated without side effects and caused statistically significant non-postural reduction of blood pressure. In less than half the patients on eitherdrug the reduction of blood pressure was clinically adequate. No attempt was made to compare the two drugs.
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Practolol
Adrenergic beta-Antagonists
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An investigation of the effectiveness of the beta adrenoceptor blocking drug oxprenolol in the treatment of primary clinical anxiety is reported. A controlled double-blind evaluation of oxprenolol versus diazepam and placebo was carried out. The results of the trial showed diazepam to be generally more effective and to produce a more rapid onset of symptom reduction than oxprenolol. The role of beta adrenergic blocking drugs in the treatment of clinical anxiety and related syndromes is discussed.
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BETA (programming language)
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