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JAMA Otolaryngology-- Head & Neck... Jul 2021Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH.
OBJECTIVE
To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020.
INTERVENTIONS
Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score.
RESULTS
Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy.
TRIAL REGISTRATION
ClinicalTrial.gov Identifier: NCT02342275.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Atenolol; China; Female; Hemangioma, Capillary; Humans; Infant; Male; Propranolol; Prospective Studies
PubMed: 33856430
DOI: 10.1001/jamaoto.2021.0454 -
AAPS PharmSciTech Nov 2021An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients...
An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating-cooling-reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C.
Topics: Atenolol; Calorimetry, Differential Scanning; Cluster Analysis; Excipients; Principal Component Analysis; Spectroscopy, Fourier Transform Infrared
PubMed: 34799781
DOI: 10.1208/s12249-021-02143-2 -
Molecules (Basel, Switzerland) Jun 2019A method based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of bisoprolol and atenolol in human bone. After the addition of...
A method based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of bisoprolol and atenolol in human bone. After the addition of lobivolol as internal standard, pulverized samples were incubated in acetonitrile for 1 h under ultrasounds. After adjusting the pH of the samples to 6, they were centrifuged, and the supernatants were subjected to solid phase extraction. Elution was achieved by using 3 mL of 2% ammonium hydroxide in 80:20 dichloromethane:isopropanol solution. Eluted samples were evaporated and derivatized. Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 0.1-0.3 ng/mg (depending on the drug) to 150 ng/mg, the mean absolute recoveries were 60% for bisoprolol and 106% for atenolol, the matrix effect was 69% for bisoprolol and 70% for atenolol and process efficiency was 41% for bisoprolol and 80% for atenolol. The intra- and inter-assay accuracy values were always better than 12%. The validated method was then applied to bone samples from two real forensic cases in which toxicological analysis in blood were positive for atenolol in the first case (0.65 µg/mL) and bisoprolol in the second case (0.06 µg/mL). Atenolol was found in bone samples from the corresponding case at the approximate concentration of 148 ng/mg and bisoprolol was found at 8 ng/mg.
Topics: Atenolol; Bisoprolol; Bone and Bones; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Reproducibility of Results; Solid Phase Extraction
PubMed: 31261852
DOI: 10.3390/molecules24132400 -
The Cochrane Database of Systematic... Oct 2014Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of... (Review)
Review
BACKGROUND
Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke.
OBJECTIVES
To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2014, Issue 5), the Database of Abstracts of Reviews of Effects (DARE) (May 2014), MEDLINE (1966 to May 2014), EMBASE (1980 to May 2014), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to May 2014). We also searched ongoing trials registers and reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism. The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the trials identified, appraised quality, and extracted data.
MAIN RESULTS
We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo and were of a high methodological quality. We noted no statistical differences among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.76 to 1.18). For other outcomes analysed (major vascular events, death from all causes, death from cardiovascular causes) , we observed no significant differences between the groups. There were minor blood pressure reductions in the intervention group. Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life. Adverse events were significantly more frequent in participants taking atenolol than in those given placebo, and were the most common reason given for discontinuing treatment (RR 1.85, 95% CI 1.45 to 2.35).
AUTHORS' CONCLUSIONS
To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.
Topics: Adrenergic beta-1 Receptor Antagonists; Atenolol; Humans; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Stroke
PubMed: 25317988
DOI: 10.1002/14651858.CD007890.pub3 -
Molecular Pharmaceutics Feb 2020The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics...
The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three β-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC-MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 μL/min, 687 μL, and 73.87 min), timolol (19.30 μL/min, 937 μL, and 33.64 min), and betaxolol (32.20 μL/min, 1421 μL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow).
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Aqueous Humor; Atenolol; Betaxolol; Chromatography, Liquid; Drug Combinations; Half-Life; Injections, Intraocular; Intraocular Pressure; Male; Metabolic Clearance Rate; Rabbits; Tandem Mass Spectrometry; Timolol; Tissue Distribution
PubMed: 31794668
DOI: 10.1021/acs.molpharmaceut.9b01024 -
European Journal of Pharmaceutics and... Sep 2021Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in...
Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUC than AUC, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.
Topics: Administration, Ophthalmic; Animals; Aqueous Humor; Atenolol; Betaxolol; Biological Availability; Drug Combinations; Ophthalmic Solutions; Outcome Assessment, Health Care; Rabbits; Solubility; Tears; Timolol; Tissue Distribution
PubMed: 34139290
DOI: 10.1016/j.ejpb.2021.06.003 -
The Journal of Veterinary Medical... May 2020This study aimed to assess the effects of atenolol on left ventricular (LV) and left atrial (LA) function in healthy cats and investigate the relationship between...
This study aimed to assess the effects of atenolol on left ventricular (LV) and left atrial (LA) function in healthy cats and investigate the relationship between atenolol administration and LA enlargement (LAE) in cats with hypertrophic cardiomyopathy (HCM). In study 1, nine experimental cats were used to assess the effects of atenolol in healthy subjects. Cats were administered one of three medication protocols for 7 days: atenolol 6.25 mg/cat twice daily, 12.5 mg/cat twice daily, or placebo (biofermin) 1 tab/cat twice daily. In study 2, cats with HCM were retrospectively recruited and divided into four groups according to atenolol administration [(control group (Cont) or atenolol administration group (Ate)] and the presence or absence of LAE as follows: Cont LAE (-) group (n=42), Cont LAE (+) group (n=20), Ate LAE (-) group (n=17), and Ate LAE (+) group (n=12). LV and LA functions were compared in both studies. LV and LA functions were decreased by atenolol administration in study 1. In study 2, the peak myocardial velocity during early diastole (E') was significantly decreased in the Cont LAE (+), Ate LAE (-), and Ate LAE (+) groups compared to that in the Cont LAE (-) group, but there were no significant differences between LAE (+) groups. Multivariate logistic analysis revealed that atenolol administration was not associated with LAE. Diastolic dysfunction may be associated with LAE; however, atenolol administration did not affect LAE in cats with HCM.
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Atenolol; Atrial Function, Left; Atrial Remodeling; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Echocardiography; Female; Male; Retrospective Studies; Ventricular Function, Left
PubMed: 32188801
DOI: 10.1292/jvms.19-0670 -
Clinical and Translational Science Apr 2016Lower melatonin level, melatonin receptor gene variations, and atenolol treatment are associated with glucose dysregulation. We investigated whether atenolol-related... (Randomized Controlled Trial)
Randomized Controlled Trial
Lower melatonin level, melatonin receptor gene variations, and atenolol treatment are associated with glucose dysregulation. We investigated whether atenolol-related glucose and melatonin changes are correlated, and whether single nucleotide polymorphisms (SNPs) in melatonin candidate genes contribute to interindividual variation in glucose change. Hypertensive Caucasians (n = 232) from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study treated with atenolol for 9 weeks were studied. Urinary 6-sulfatoxymelatonin (aMT6s) was measured pre- and posttreatment and normalized to urinary creatinine. Pharmacogenetic effects on glucose change of 160 SNPs in 16 melatonin candidate genes were assessed with multiple linear regression. Atenolol was associated with increased glucose (1.8 ± 10.1mg/dl, P = 0.02) and decreased aMT6s (-4.5 ± 10.1 ng/mg, P < 0.0001). However, the aMT6s change was not correlated with post-atenolol glucose change. SNP rs11649514 in PRKCB was associated with glucose change (P = 1.0×10(-4)). PRKCB is involved in the melatonin-insulin regulatory pathway, and may be important in mediating clinically meaningful atenolol-related hyperglycemia.
Topics: Atenolol; Blood Glucose; Fasting; Female; Glucose; Humans; Male; Melatonin; Middle Aged; Polymorphism, Single Nucleotide; Protein Kinase C beta; Signal Transduction; White People
PubMed: 26946962
DOI: 10.1111/cts.12389 -
Ecotoxicology and Environmental Safety Apr 2021MoS/montmorillonite (MoS/Mt) composite was successfully synthesized through a simple hydrothermal method, and its adsorption performance for two emerging...
The adsorption performance and micro-mechanism of MoS/montmorillonite composite to atenolol and acebutolol: Adsorption experiments and a novel visual study of interaction.
MoS/montmorillonite (MoS/Mt) composite was successfully synthesized through a simple hydrothermal method, and its adsorption performance for two emerging contaminants-atenolol (ATE) and acebutolol (ACE) was researched. The batch experiments revealed that the adsorption process can be described by the Pseudo-second order model and Langmuir model, and the adsorption capacity of MoS/Mt, MoS and Mt for ATE were 132.08 mg/g, 60.68 mg/g and 74.23 mg/g, for ACE were 113.82 mg/g, 33.01 mg/g and 36.05 mg/g, respectively. Besides, Fourier-transform infrared spectroscopy (FTIR), BET specific surface area measurement and X-ray photoelectron spectroscopy (XPS) were also employed to analyze the adsorption mechanism. Moreover, quantitative molecular surface analysis and weak intermolecular interaction analysis with independent gradient model were combined to probe the microscopic interaction between the adsorbent and adsorbate. The results indicated the interactions included hydrogen bonding and vdW interaction. Mt and MoS interacted more strongly with ATE than ACE, which revealed the reason MoS/Mt, Mt and MoS possessed higher adsorption capacity for ATE.
Topics: Acebutolol; Adsorption; Atenolol; Bentonite; Hydrogen Bonding; Hydrogen-Ion Concentration; Kinetics; Molybdenum; Photoelectron Spectroscopy; Spectroscopy, Fourier Transform Infrared; Water Pollutants, Chemical
PubMed: 33578102
DOI: 10.1016/j.ecoenv.2021.111993 -
American Journal of Hypertension Mar 2012Thiazides and β-blockers cause adverse metabolic effects (AMEs), but whether these effects share predictors with blood pressure (BP) response is unknown. We aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Thiazides and β-blockers cause adverse metabolic effects (AMEs), but whether these effects share predictors with blood pressure (BP) response is unknown. We aimed to determine whether AMEs are correlated with BP response in uncomplicated hypertensives.
METHODS
In a multicenter, open-label, parallel-group trial, we enrolled 569 persons, aged 17-65, with random assignment to 9 weeks of daily hydrochlorothiazide (HCTZ) or atenolol monotherapy, followed by 9 weeks of add-on therapy with the alternate agent. Measurements included home BP, averaged over 1 week, weight and fasting levels of serum glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and uric acid (UA) before and after monotherapy and after add-on therapy.
RESULTS
Increases in UA correlated with reductions in systolic BP (SBP) (r = -0.18; P = 0.003) and diastolic BP (DBP) (r = -0.20; P = 0.001) following HCTZ monotherapy and add-on therapy (r = -0.27 and r = -0.21, respectively; both P < 0.001). After adjustment for age, race, gender, and baseline body mass index (BMI), only the correlation between UA and DBP response became nonsignificant. Reductions in HDL correlated with systolic response following atenolol monotherapy (r = 0.18; P = 0.002) and with systolic and diastolic response following add-on therapy (r = 0.30 and r = 0.24, respectively; both P < 0.0001). These correlations remained significant after covariate adjustment. BP responses were not correlated with changes in glucose, LDL, triglycerides, or weight following either therapy.
CONCLUSIONS
BP response correlated with changes in UA following HCTZ therapy and HDL following atenolol therapy. No other significant correlations were observed between BP response and AMEs, suggesting that these effects generally do not share predictors. Patients should be monitored for AMEs, regardless of BP response.
Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Atenolol; Blood Glucose; Blood Pressure; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Triglycerides; Uric Acid
PubMed: 22089105
DOI: 10.1038/ajh.2011.215