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American Heart Journal May 1985Acebutolol was compared to atenolol in 33 patients with mild to moderate essential hypertension (diastolic blood pressure greater than 95 mm Hg) with the use of a... (Clinical Trial)
Clinical Trial Comparative Study
Acebutolol was compared to atenolol in 33 patients with mild to moderate essential hypertension (diastolic blood pressure greater than 95 mm Hg) with the use of a double-blind crossover study design. At 8 weeks of treatment, acebutolol, 400 mg once daily, and atenolol, 100 mg once daily, produced similar significant (p less than 0.01) reductions in average mean arterial blood pressure (12% and 11%, respectively) from baseline. Average heart rate at 4 weeks was also significantly reduced (p less than 0.01) from baseline (acebutolol, 14.8%; atenolol, 18.3%); the reduction with acebutolol, however, was significantly less (p less than 0.05) than that seen with atenolol. Both agents produced similar effects during exercise, and serum drug determinations showed acebutolol to be rapidly metabolized. Acebutolol appeared to be better tolerated: the frequency of side effects with acebutolol (24%) was less than with atenolol (45%). Acebutolol is as effective as atenolol in mild to moderate essential hypertension. Acebutolol appears to be better tolerated and to have a lesser effect on heart rate than atenolol.
Topics: Acebutolol; Adult; Aged; Atenolol; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged
PubMed: 3993534
DOI: 10.1016/0002-8703(85)90705-7 -
Anaesthesia Nov 1982Plasma levels of acebutolol and its major human metabolite, diacetolol, were determined before, during and after aortocoronary bypass grafting in 10 patients who had...
Plasma levels of acebutolol and its major human metabolite, diacetolol, were determined before, during and after aortocoronary bypass grafting in 10 patients who had received a chronic oral regimen of acebutolol 200 mg t.d.s. for at least 6 days before surgery, a 200 mg dose with the premedication and 5-10 mg intravenously immediately before intubation. It was found that this regimen produced beta-adrenoceptor antagonist levels which were within the range in which attenuation of hypertension and tachydysrhythmia occurs. These effective plasma levels were sustained throughout surgery and persisted into the early recovery period.
Topics: Acebutolol; Adult; Coronary Artery Bypass; Humans; Intraoperative Period; Male; Middle Aged; Postoperative Period; Premedication; Time Factors
PubMed: 6982635
DOI: 10.1111/j.1365-2044.1982.tb01751.x -
Journal of Pharmaceutical Sciences Apr 1991The chiral beta-blocker acebutolol (AC) is marketed as a racemic mixture. Both AC and its major metabolite, diacetotol (DC), are chiral, the S-enantiomer possessing...
The chiral beta-blocker acebutolol (AC) is marketed as a racemic mixture. Both AC and its major metabolite, diacetotol (DC), are chiral, the S-enantiomer possessing beta-blocking activity. The pharmacokinetics of AC and DC enantiomers was determined in 12 healthy subjects following oral administration of 200 mg of AC. Plasma and urine were collected over a 24-hr period and both AC and DC enantiomers were measured utilizing a stereospecific HPLC assay. Concentrations of S-AC were predominant in both plasma and urine [AUC S:R, 1.20 +/- 0.1; cumulative urinary excretion (sigma Xu) S:R, 1.17 +/- 0.05), which corresponded to a significantly greater oral clearance of R-AC (106 +/- 30 L/h) than S-AC (87 +/- 22 L/h). The Cmax of R-DC was significantly greater than for S-DC (S/R 0.7 +/- 0.1). The half-life (t1/2) of R-DC (6.4 +/- 1.6 h) was significantly shorter than that of S-DC (8.8 +/- 2.4 h). The observed AUC values for R- and S-DC were not significantly different. Renal clearance of R-DC (70 +/- 34 mL/min) was significantly greater than that of S-DC (53 +/- 29 mL/min). The data suggest that the first-pass metabolism of R-AC to R-DC is stereoselective. This metabolism, coupled with the stereoselective renal excretion of R-DC is likely a major contributor to the observed stereoselective disposition of AC and its major metabolite in humans.
Topics: Acebutolol; Administration, Oral; Adult; Female; Humans; Male; Stereoisomerism
PubMed: 1865329
DOI: 10.1002/jps.2600800405 -
British Medical Journal (Clinical... Oct 1981Systolic blood pressure, heart rate, and blood glucose concentration were measured in the first three days of life in 10 infants born to mothers who had received...
Systolic blood pressure, heart rate, and blood glucose concentration were measured in the first three days of life in 10 infants born to mothers who had received acebutolol, a cardioselective beta-adrenergic-blocking agent, for hypertension in pregnancy and compared with values in 10 infants whose mothers had received methyldopa. The blood pressure was expressed as a percentage of the expected value. Blood pressure was significantly lower in the infants of the mothers given acebutolol (p less than 0.02, less than 0.01, and less than 0.01 respectively during the three days of observation). Heart rate was also lower, but the significance was only at the 0.05 level. Blood glucose was not significantly different between the two groups. These results suggest that care should be taken in prescribing beta-adrenergic-blocking drugs during pregnancy.
Topics: Acebutolol; Blood Glucose; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Infant, Newborn; Maternal-Fetal Exchange; Methyldopa; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies
PubMed: 6794766
DOI: 10.1136/bmj.283.6299.1077 -
European Journal of Clinical... Dec 1978
Clinical Trial
Topics: Acebutolol; Acetylation; Adult; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Placebos; Pulse; Renin; Time Factors
PubMed: 367793
DOI: 10.1007/BF00716378 -
Endocrinologia Japonica Jun 1988A patient with essential hypertension receiving the oral administration of acebutolol, a beta 1-selective adrenergic blocker, showed a marked increase in urinary...
A patient with essential hypertension receiving the oral administration of acebutolol, a beta 1-selective adrenergic blocker, showed a marked increase in urinary 17-ketosteroid (17-KS) excretion determined by Zimmermann's method. Since the normal concentration of each fraction of 17-KS was found in this case by gas chromatography, the possibility of an abnormality in steroid metabolism could be excluded from the mechanism of the increase in the measured value for urinary 17-KS. In the urine samples from patients treated with acebutolol, acebutolol and acetylated acebutolol, a main metabolite of acebutolol, were found equally among them. Moreover, acebutolol or acetylated acebutolol resulted in a dose-dependent increase in 17-KS by Zimmermann's method in phosphate buffered saline or in a urine sample. However, the other beta-blockers, such as propranolol, alprenolol and oxprenolol did not show any effect on the determined value for urinary 17-KS. Thus it was concluded that the activated methylene group of acebutolol and acetylated acebutolol may interfere with the measured values obtained by Zimmermann's method.
Topics: 17-Ketosteroids; Acebutolol; Drug Interactions; Female; Humans; Hypertension; Methods; Middle Aged
PubMed: 3197660
DOI: 10.1507/endocrj1954.35.485 -
Annals of Internal Medicine Sep 1981
Topics: Acebutolol; Antibodies; Antibodies, Antinuclear; DNA; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged
PubMed: 6973944
DOI: 10.7326/0003-4819-95-3-326 -
Therapie 1995
Review
Topics: Acebutolol; Acute Disease; Antihypertensive Agents; Female; Humans; Middle Aged; Suicide, Attempted
PubMed: 8745963
DOI: No ID Found -
The American Journal of Cardiology Aug 1988
Clinical Trial Comparative Study
Topics: Acebutolol; Angina Pectoris; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Physical Exertion; Random Allocation; Syndrome; Verapamil
PubMed: 3041793
DOI: 10.1016/0002-9149(88)90232-9 -
Biochemical Pharmacology Dec 2015Acebutolol, a β-adrenergic receptor-blocker, occasionally causes drug-induced lupus erythematosus (DILE). Acebutolol is mainly metabolized to diacetolol. Because...
Acebutolol, a β-adrenergic receptor-blocker, occasionally causes drug-induced lupus erythematosus (DILE). Acebutolol is mainly metabolized to diacetolol. Because metabolic activation has been considered to be related to acebutolol-induced toxicity, we sought to identify the enzymes that are responsible for acebutolol metabolism and investigate their involvement in acebutolol-induced toxicity. By using human liver microsomes (HLM) or intestinal microsomes and recombinant enzymes, we found that diacetolol was produced via hydrolysis by carboxylesterase 2 (CES2) and subsequent acetylation by N-acetyltransferase 2 (NAT2). When acetolol, a hydrolytic metabolite of acebutolol, was incubated with HLM and an NADPH-generating system, a metabolite conjugated with N-acetylcystein was generated. This metabolite was found to be formed by CYP2C19 based on studies with a panel of recombinant cytochrome P450 enzymes and an inhibition study using HLM with tranylcypromine, a CYP2C19 inhibitor. Because antinuclear antibody (ANA) production is associated with DILE, we investigated whether ANA was detected in plasma from mice treated with acebutolol. Administration of acebutolol (100mg/kg, p.o.) to female C57BL/6 mice for 30 days resulted in ANA production in plasma in seven of thirteen mice. The number of mice that showed ANA production was larger in mice co-treated with pregnenolone 16α-carbonitrile, an inducer of P450s, whereas it was lower in mice co-treated with tri-o-tolylphosphate or 1-aminobenzotriazole, which are inhibitors of esterases or P450s, respectively. These results suggested that the hydrolysis and oxidation of acebutolol was associated with ANA production. In summary, this study demonstrated that metabolic activation may be a causal factor of adverse reactions of acebutolol.
Topics: Acebutolol; Adult; Animals; Antibodies, Antinuclear; Carboxylesterase; Cytochrome P-450 CYP2C19; Dose-Response Relationship, Drug; Female; Humans; Male; Mice; Mice, Inbred C57BL; Microsomes, Liver; Young Adult
PubMed: 26408002
DOI: 10.1016/j.bcp.2015.09.016