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British Journal of Clinical Pharmacology Oct 19771 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each...
1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady-state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/- 1.0. 4 Previous studies using non-specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.
Topics: Acebutolol; Administration, Oral; Arrhythmias, Cardiac; Humans; Time Factors
PubMed: 911602
DOI: 10.1111/j.1365-2125.1977.tb00779.x -
La Nouvelle Presse Medicale Dec 1975Pharmacodynamic data correlating beta-adrenoceptor blockade with plasma level of drug were obtained in healthy male volunteers (3). Direct comparison of the inhibition... (Clinical Trial)
Clinical Trial
Pharmacodynamic data correlating beta-adrenoceptor blockade with plasma level of drug were obtained in healthy male volunteers (3). Direct comparison of the inhibition of isoprenaline induced tachycardia was achieved in each volunteer after the administration of single doses of either acebutolol (300 mg), practolol (400 mg) or propranolol (40 mg). These drugs were approximately equipotent at these doses, at the times of maximum beta-adrenoceptor blockade. Pharmacokinetic data were obtained in hypertensive male patients (4) after treatment with 14C-radioactively labelled acebutolol hydrochloride. Both 'total-14C' levels and specific '14C-acebutol' levels were determined in plasma, urine and faeces. It was shown, by calculation from the renal clearance, that the late biological half-life for the decline of 14C-acebutolol in plasma was 9.4 h and 13.2 h, respectively, in two of these patients treated with a single oral dose (200 mg) of 14C-acebutolol hydrochloride. In one of the patients treated by intravenous infusion (20 mg/10 mn), the late biological half-life plasma was calculated to be 7.5 h. Renal clearance of acebutolol was shown to be close to a mean of 83 ml plasma/mn for each of three patients (two oral and one intravenous) in spite of the fact that one of the orally treated patients had an elevated level of urea in his plasma (47 mg/100 ml) indicative of some impairment of kidney function. The recovery of 14C-radioactivity in the urine (29 p. cent) and faeces (64 p. cent) was 93 p.cent of the dose of labelled acebutolol in one of the orally treated patients. The overall proportion of the dose excreted as unchanged 14C-acebutolol was 62 p.cent. The major metabolite was the product formed by shortening of the butyramido-group of acebutolol to form an acetamido-group. This metabolite was also readily excreted in both urine and faeces and was also detected in an extract of the 4 h plasma from an orally treated patient. It was identified by co-chromatography as the acetyl analogue (M & B 16 942) of acebutolol. It would be detected by the colorimetric assay of acebutolol in plasma because the same aromatic amino-compound (M & B 17 127) would be formed during the acid hydrolysis procedure. A small quantity of an other unidentified metabolite was detected in an extract of freeze-dried urine after autoradiography of a two dimensional thin layer silica-gel chromatogram.
Topics: Acebutolol; Animals; Autoradiography; Clinical Trials as Topic; Half-Life; Humans; Hypertension; Male; Practolol; Propranolol; Rats
PubMed: 768905
DOI: No ID Found -
Journal of Labelled Compounds &... Aug 2014Acebutolol was successfully labeled with (125) I via direct electrophilic substitution reaction. Radioiodinated acebutolol was prepared with a maximum radiochemical...
Acebutolol was successfully labeled with (125) I via direct electrophilic substitution reaction. Radioiodinated acebutolol was prepared with a maximum radiochemical yield of 96.5 ± 0.3% and in vitro stability up to 72 h. The in vivo biological distribution of radioiodinated acebutolol showed high heart uptake of 37.8 ± 0.14% injected activity/g organ with low lungs and liver uptakes at 5 min post-injection. In vivo receptor blocking study was carried out in mice to evaluate its selectivity to heart. Radioiodinated acebutolol showed fast heart accumulation with high heart/liver ratio, which provides the ability for fast myocardial imaging with significant decrease in the radiation hazards risk on patients. So, radioiodinated acebutolol could be displayed as a radiotracer drug of choice in case of emergency patients for myocardial perfusion imaging.
Topics: Acebutolol; Animals; Iodine Radioisotopes; Male; Mice; Myocardial Perfusion Imaging; Radiopharmaceuticals; Tissue Distribution
PubMed: 25196119
DOI: 10.1002/jlcr.3223 -
British Journal of Clinical Pharmacology Oct 19781. Eleven hypertensive patients were studied in a double-blind comparison of acebutolol, a beta-adrenoceptor blocker, and placebo. 2. Optimum dosage defined in an open... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1. Eleven hypertensive patients were studied in a double-blind comparison of acebutolol, a beta-adrenoceptor blocker, and placebo. 2. Optimum dosage defined in an open assessment varied from 200--600 mg twice daily. 3. Blood pressure and pulse rate fell significantly while patients were lying, standing and after exercise. 4. Blood pressure remained as well controlled on each patient's optimum daily dose when taken once daily, and assessed 24 h post dose. 5. There was no correlation between blood pressure reduction and changes in heart rate. On once daily therapy while blood pressure remained unchanged at 24 h post dose there was a signficant reduction in beta-adrenoceptor blockade as measured by percentage reduction in exercise tachycardia. 6. There was no significant change in urinary catecholamine excretion or echocardiographically estimated cardiac output. 7. A correlation was found between the change in plasma renin activity (log transformed) and blood pressure reduction.
Topics: Acebutolol; Adult; Aged; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Echocardiography; Female; Humans; Hypertension; Male; Middle Aged; Placebos; Pulse
PubMed: 359018
DOI: 10.1111/j.1365-2125.1978.tb00863.x -
International Journal of Legal Medicine Jan 2020Acebutolol is a β1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is...
Acebutolol is a β1-selective adrenergic receptor antagonist with moderate membrane-stabilizing activity and intrinsic sympathomimetic activity; accordingly, the drug is indicated in hypertension, angina pectoris, and arrhythmia. However, acebutolol's beta-blocking properties also extend the QRS and QTc intervals, and may predispose the patient to ventricular tachydysrhythmia. Here, we report autopsy and toxicological findings on a fatal case of acebutolol self-poisoning in a 70-year-old woman. Toxicological analyses of post-mortem samples (using a liquid chromatography high-resolution mass spectrometry (LC-HR-MS) method) highlighted high concentrations of acebutolol and its metabolite diacetolol in femoral blood (92.8 mg/L and 21.2 mg/L, respectively) and other matrices (cardiac blood, urine, bile, and gastric contents). A molecular networking approach provided useful information on acebutolol's metabolism and revealed the existence of an unknown phase II metabolite of acebutolol. Molecular networking also facilitated visualization of the complex LC-HR-MS/MS datasets and the sample-to-sample comparisons that confirmed massive acebutolol intoxication by ingestion.
Topics: Acebutolol; Aged; Autopsy; Chromatography, Liquid; Female; Humans; Molecular Imaging; Suicide; Tandem Mass Spectrometry
PubMed: 30997571
DOI: 10.1007/s00414-019-02062-9 -
Skin Pharmacology and Physiology 2005Beta-blocking medications are rarely associated with drug-induced lupus erythematosus syndrome and have never been incriminated as a cause of subacute lupus...
Beta-blocking medications are rarely associated with drug-induced lupus erythematosus syndrome and have never been incriminated as a cause of subacute lupus erythematosus (SCLE). We present herein the first case of SCLE induced by acebutolol. A 57-year-old woman presented with a 1-month history of a cutaneous eruption of the photo-exposed areas. One month ago, the patient had started a treatment with oral acebutolol to cure a hypertension of 1-year evolution. Physical examination revealed erythematous scaly annular plaques, involving the face, arms and trunk. Immunologic serology findings revealed a positive titer of antinuclear antibodies up to 1/1,280 with positivity of antihistone and Ro/SSA antibodies. Acebutolol was stopped, and the lesions cleared completely 4 months later. Literature data, along with our case, suggest a link between acebutolol therapy and the onset of a lupus syndrome. Although this is the first report of acebutolol-induced SCLE, we should be aware of this occurrence, and avoidance of acebutolol is recommended in patients with stigmata of lupus erythematosus.
Topics: Acebutolol; Adrenergic beta-Antagonists; Antibodies, Antinuclear; Female; Humans; Hypertension; Lupus Erythematosus, Cutaneous; Middle Aged
PubMed: 16015021
DOI: 10.1159/000086668 -
Journal of Analytical Toxicology 1992A fatal case of acebutolol self-poisoning is presented. After single-step liquid-liquid alkaline extraction, acebutolol was identified by using an HPLC/DAD screening... (Review)
Review
A fatal case of acebutolol self-poisoning is presented. After single-step liquid-liquid alkaline extraction, acebutolol was identified by using an HPLC/DAD screening procedure. By means of a specific HPLC method, acebutolol was then quantified in a large range of postmortem samples. The blood acebutolol concentration was 34.7 micrograms/mL. The tissue distribution of the drug is discussed in the light of the existing literature.
Topics: Acebutolol; Adolescent; Chromatography, High Pressure Liquid; Female; Humans; Suicide
PubMed: 1293408
DOI: 10.1093/jat/16.6.398 -
Clinical Pharmacology and Therapeutics Nov 1977The disposition of acebutolol has been studied following intravenous doses of 0.25 to 1.0 mg/kg in 9 healthy subjects using a specific chromatographic assay to determine...
The disposition of acebutolol has been studied following intravenous doses of 0.25 to 1.0 mg/kg in 9 healthy subjects using a specific chromatographic assay to determine concentrations of drug in blood. The mean blood clearance was 6.55 ml/min/kg and the mean renal clearance, 2.68 ml/min/kg. Blood clearance was found to have a coefficient of variation of 14% for the group, to be independent of dose, and to remain essentially constant over approximately 3 wk. The fraction of the dose excreted in the urine unchanged was 0.405. Data were fitted to an equation for a two-compartment model. The mean fast and slow half-lives were 6.08 and 156.8 min, respectively. The volume of the central compartment was 0.223 L/kg, and the volume of distribution at steady-state was 1.165 L/kg. The fraction of acebutolol unbound to plasma proteins was 0.743 and was independent of drug concentration in the range examined. Data obtained from 15-min infusions were used to predict plateau blood concentrations with good accuracy during an 8-hr dosage regimen.
Topics: Acebutolol; Adult; Humans; Infusions, Parenteral; Kidney; Kinetics; Metabolic Clearance Rate; Models, Biological; Protein Binding; Time Factors
PubMed: 913023
DOI: 10.1002/cpt1977225part1557 -
Ugeskrift For Laeger May 1983
Topics: Acebutolol; Adrenergic beta-Antagonists; Chemical Phenomena; Chemistry; Heart Diseases; Humans
PubMed: 6136109
DOI: No ID Found -
American Heart Journal May 1985The clinical pharmacology and pharmacokinetics of acebutolol are summarized. Acebutolol and its longer-acting metabolite, diacetolol, are rapidly absorbed into the...
The clinical pharmacology and pharmacokinetics of acebutolol are summarized. Acebutolol and its longer-acting metabolite, diacetolol, are rapidly absorbed into the circulation from the gastrointestinal tract, and their bioavailability, unlike that of propranolol and metoprolol, is not significantly altered by whether the patient has recently eaten. Acebutolol is extensively metabolized by the liver, and elimination pathways involve approximately 30% to 40% through renal excretion and 50% to 60% by nonrenal mechanisms, including the bile and direct passage through the intestinal wall. The decreased hepatic metabolism and renal clearance rates seen in elderly patients may lead to the accumulation of both acebutolol and its metabolite, as has been reported with propranolol. In studies conducted to ascertain acebutolol's possible effect on common concurrently administered medications, the drug did not significantly alter either serum digoxin levels or serum insulin levels in diabetic patients treated with tolbutamide, nor did it change prothrombin time in patients treated with sodium warfarin.
Topics: Acebutolol; Adrenergic beta-Antagonists; Adult; Aged; Digoxin; Drug Interactions; Female; Humans; Hypertension; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Prothrombin Time; Tolbutamide; Warfarin
PubMed: 2859776
DOI: 10.1016/0002-8703(85)90697-0