Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new coreg research articles will be listed here shortly after becoming available to us.
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J Cardiovasc Pharmacol. 2008 Jun 26;
Alfieri AB, Briceno L, Fragasso G, Spoladore R, Palloshi A, Bassanelli G, Montano C, Arioli F, Cuko A, Ruotolo G, Margonato A
Neuroendocrine/inflammatory and endothelial functions have been indicated as crucial for heart failure (HF) patients. We evaluated relation in HF patients among cytokines and asymmetric dimethylarginine (ADMA) and left ventricular ejection fraction (LVEF) at baseline and after long-term administration of carvedilol. Interleukin 10 (IL-10), interleukin 18 (IL-18), and ADMA were measured in 22 NYHA class II to IV HF patients at baseline and after 40 +/- 14 months of carvedilol treatment. Patients were divided into 2 groups according to whether, after treatment with carvedilol, LVEF had increased at least 5% (responders) or less than 5% (non-responders). In responders (11 of 22 patients), LVEF increased from 38 +/- 6% to 50 +/- 7%, (P < 0.001); in non-responders, it decreased from 36 +/- 9% to 31 +/- 6%, (P = 0.02); NYHA class significantly decreased in both groups. IL-18 decreased in responders (from 586.4 +/- 128 to 183.13 +/- 64.4 pg/mL; P < 0.001) and in non-responders (from 529.3 +/- 116.25 to 142.4 +/- 58.9 pg/mL; P < 0.001). IL-10 increased in responders (from 0.49 +/- 0.25 to 2.01 +/- 1.01 pg/mL; P < 0.001) and in non-responders (from 0.64 +/- 0.31 to 1.33 +/- 0.59 pg/mL; P < 0.001). Conversely, ADMA levels decreased only in responders (from 0.67 +/- 0.16 to 0.44 +/- 0.15 mumol/L; P < 0.001), and an inverse correlation was observed between basal ADMA levels and changes in LVEF after treatment. In HF patients, carvedilol appears to reduce symptoms and the expression of inflammation, regardless of the LV functional response. In those patients showing improvement of LVEF, the reduction of inflammation is paralleled by a reduction of ADMA. We surmise that carvedilol could be effective at various independent levels as a result of possible pleiotropic effects of this agent.
J Cardiovasc Pharmacol Ther. 2008 Jul 1;
Crespo MJ, Cruz N, Altieri PI, Escobales N
To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.
Flow injection spectrofluorimetric determination of carvedilol mediated by micelles.
Talanta. 2008 Jun 30; 76(1): 166-71
Silva RA, Wang CC, Fernández LP, Masi AN
A novel flow injection (FI)-spectrofluorimetric methodology for the determination of carvedilol in microheterogeneous medium has been developed. In the sodium dodecyl sulfate (SDS) surfactant medium, an additional fluorescence enhancement was produced by the electrolyte NaCl. A total enhancement of 3.1-fold in the native fluorescent response was achieved respect to aqueous medium. Using an excitation and emission wavelength of 286 and 341 nm, respectively, a good linear relationship was obtained in the range of 9x10(-8) to 1x10(-6) mol L(-1) with a detection limit of 3.63x10(-9) mol L(-1) (S/N=3). This method was applied to determine carvedilol in commercial pharmaceutical formulations. Good concordance was found between the nominal (6.25, 12.5 and 25.0 mg) and experimental values. The new methodology developed showed high selectivity respect to the common excipients used in pharmaceuticals. The sampling rate was 30 samples h(-1). From the fluorescent properties, binding constant for carvedilol-SDS determined was 3.2x10(2) L mol(-1).
HPLC analysis, isolation and identification of a new degradation product in carvedilol tablets.
J Pharm Biomed Anal. 2008 May 16;
Galanopoulou O, Rozou S, Antoniadou-Vyza E
Carvedilol (CV) is an antagonist of alpha(1) and beta(1),beta(2) membrane adrenoceptors and also a modulator of cardiac electrophysiological properties. It is widely prescribed for the treatment of cardiovascular diseases. During stability testing of CV solid dosage forms an unknown degradation product referred as UP, exceeded the identification thresholds of ICH Q3B guidelines. The HPLC analysis of the detected unknown product was performed by a newly, developed, specific and validated method, also suitable for the quantitative determination of the known CV impurities (imp B, C, E and F) and the other degradation products. The separation was achieved with an X-terra C(18) column, using acetonitrile-phosphate buffer pH 2.5 as mobile phase. The isolation of UP was carried out by semi-preparative chromatography method, followed by deep freezing of the collected fractions until the organic and the aqueous phases were separated. Chromatographic behaviour of CV and UP was compared, in mobile phases of different pH and gave valuable information concerning the dissimilarities of their ionization. UP was further studied by MS and (1)H NMR spectrometry, revealing structural similarities with the parent molecule. Finally, the unknown peak of degradation product was attributed to a new compound generated from the interaction of CV molecule and polyvinyl pyrrolidone (PVP) in the presence of water molecules. Moisture and temperature was proved to affect the formation of UP and its concentration in CV tablets. Appropriate modifications of the packaging of CV tablets can be made in order to reduce UP concentration down to the accepted levels, during the tablets' shelf life.
[Evaluation of the effect of carvedilol in children with dilated cardiomyopathy]
Arch Cardiol Mex. 2008 Jan-Mar; 78(1): 52-9
Saucedo NA, Alarcón AV, Islas GE, De La Cruz LR
OBJECTIVE: To evaluate the effect of carvedilol administrated during 8 months in children with heart failure secondary to dilated cardiomyopathy. METHODS: We initiated carvedilol in patients who, despite optimization of standard treatment, had persistent left ventricular ejection fraction < or = 40% and evaluated the systolic and diastolic left ventricular function before and after 4 and 8 months of treatment. RESULTS: 19 patients were included in the study, 10 women; median age: 6.7 years and 17 +/- 12.4 months after the diagnosis. The ejection fraction improved significantly from entry to eight months (median: 33.5 to 52.6%, p = 0.01) as did the shortening fraction (m: 14.8 to 25.8%, p = 0.01). The myocardial performance index abnormal in all 19 patients became normal in 5 at the end of study. In addition mitral Doppler flow which was altered in 9 improved in 3 and pulmonary venous flow abnormal in all patients improved in 13. Only 1 patient presented minimal adverse effects. CONCLUSIONS: Carvedilol added to standard therapy for dilated cardiomyopathy improves left ventricular function, is well tolerated, and has minimal adverse effects in childhood.
Liver Transpl. 2008 Jun 25; 14(7): 1020-1028
Galioto A, Semplicini A, Zanus G, Fasolato S, Sticca A, Boccagni P, Frigo AC, Cillo U, Gatta A, Angeli P
The aim of this study was to compare nifedipine and carvedilol in the treatment of de novo arterial hypertension after orthotopic liver transplantation (OLT). The study included 50 patients who developed arterial hypertension after OLT. Twenty-five patients received nifedipine (group A), and 25 received carvedilol (group B). Patients were defined as intolerant to nifedipine or carvedilol if severe adverse effects developed. These patients stopped the first drug and were switched to the other one. Patients were defined as full responders to monotherapy if there was normalization of blood pressure, and they were defined as partial responders by the need to add a second antihypertensive drug, ramipril. The 2 groups of patients were similar for baseline conditions. At the end of the study, patients intolerant to monotherapy were 48% of group A and 12.5% of group B (P < 0.01). Full responders were 20% of group A and 33.33% of group B (P < 0.01). Partial responders were 22% of group A and 54.1% of group B (P < 0.01). The addition of ramipril normalized blood pressure in 19% of partial responders to monotherapy (75% in partial responders to nifedipine and 30% in partial responders to carvedilol, P < 0.01). In responders to either monotherapy or combined therapy, there was a significant improvement of renal function. In responders to carvedilol, but not in responders to nifedipine, the daily dose of tacrolimus at 1 year should be reduced to 50% compared to the baseline dose to maintain the blood trough level in the therapeutic range. Liver Transpl 14:1020-1028, 2008. (c) 2008 AASLD.
Eur J Heart Fail. 2008 Jun 17;
Macchia A, Monte S, Pellegrini F, Romero M, D'Ettorre A, Tavazzi L, Tognoni G, Maggioni AP
AIMS: To assess the relationship between depression and clinical outcomes among elderly patients with heart failure (HF) in a community setting. METHODS AND RESULTS: To identify patients with HF and depression we used record linkage analysis of hospital discharge records, prescription databases and vital statistics. All consecutive patients aged>/=60 years in 6 Local Health Authorities in Italy were included. HF was defined as either: 1) hospital discharge with HF diagnosis (ICD-9: 428) and/or 2) chronic treatment for HF identified as concomitant (within 45 days) prescription of any combination of ACE inhibitors, digoxin, furosemide, bisoprolol, carvedilol, spironolactone, ARB-blockers. Depression was identified from exposure to psychotropic drugs before HF diagnosis. Cox proportional hazards models adjusted for major confounders were used. To adjust for potential residual known confounders, a propensity score analysis was performed. Sensitivity and subgroup analysis were used to demonstrate the consistency or robustness of the results. 48,117 patients with HF were identified. Of these, 3328 (6.9%) were treated for depression. Among patients with HF, those with depression were significantly older, and more likely to be women with a previous stroke. Depression significantly worsened major outcomes including all cause mortality [HR (95%CI); 1.20 (1.08-1.33)] and the composite of stroke/TIA/AMI [1.23 (1.13-1.34)]. Patients with depression had no increased risk of rehospitalisation for HF. Propensity scores and subgroup analysis confirmed these findings. CONCLUSION: Among elderly patients with HF, depression was independently associated with poor clinical outcomes mostly due to an increase in vascular events.
Diabetes Obes Metab. 2008 Jun 17;
Bell DS, Bakris GL, McGill JB
Context: Vasoconstricting beta-blocker use is associated with a reduction in HDL cholesterol, higher triglyceride, total cholesterol and LDL cholesterol levels, whereas carvedilol, a vasodilating beta-blocker, has not been associated with these effects. Objective: To compare in a randomized, double-blind study, the effects of the beta 1-blocker metoprolol tartrate with the combined alpha 1, beta-blocker carvedilol on serum lipid concentrations. Methods: A prospective randomized, double-blind, parallel-group trial compared the effects of carvedilol and metoprolol on total cholesterol, triglycerides, calculated LDL, HDL and non-HDL cholesterol levels at baseline and after 5 months of therapy as a secondary objective in the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensive (GEMINI) study. In this study, 1235 participants with type 2 diabetes and hypertension who were receiving renin-angiotensin system blockers were randomized either to carvedilol, receiving 6.25-25 mg twice daily, or to metoprolol tartrate, receiving 50-200 mg twice daily. If needed, hydrochlorothiazide and a dihydropyridine calcium channel blocker were added to achieve blood pressure goals. Results: In the metoprolol tartrate group, triglycerides and non-HDL cholesterol increased and both the LDL and the HDL cholesterol levels decreased. In the carvedilol group, total LDL and HDL cholesterol decreased, non-HDL cholesterol was unchanged and triglycerides increased. Comparing the carvedilol and metoprolol tartrate groups, there was no statistically significant difference in LDL and HDL cholesterol levels, but there was a significantly greater decreases with carvedilol in total cholesterol [-2.9%, 95% confidence interval (CI) -4.60 to -1.15, p < 0.001], triglycerides (-9.8%, 95% CI -13.7, -5.75%, p < 0.001) and non-HDL cholesterol (-4.03%, 95% CI -6.3 to -1.8, p < 0.0006). At the end of the study, significantly more participants in the metoprolol tartrate group had had initiation of statin therapy or the statin dose increased than those in the carvedilol group (11 vs. 32%, p = 0.04). Conclusions: In patients with type 2 diabetes currently receiving a renin-angiotensin blocker, compared with metoprolol tartrate, the addition of carvedilol for blood pressure control resulted in a significant decrease in triglyceride, total cholesterol and non-HDL cholesterol levels. The use of metoprolol resulted in a significantly greater rate of initiation of statin therapy or an increase in the dose of existing statin therapy when compared with carvedilol utilization.
Pharmacokinetic/pharmacodynamic modeling of the cardiovascular effects of beta blockers in humans.
Arch Pharm Res. 2008 Jun; 31(6): 814-21
Baek IH, Yun MH, Yun HY, Kwon KI
Pharmacokinetic-pharmacodynamic (PK/PD) analysis is useful study in clinical pharmacology, also PK/PD modeling is major tools for PK/PD analysis. In this study, we sought to characterize the relationship between the cardiovascular effects and plasma concentrations of the beta blocker drugs carvedilol and atenolol using PK/PD modeling in healthy humans. One group received oral doses of atenolol (50 mg) and the other group received oral doses of carvedilol (25 mg). Subsequently, blood samples were taken, and the effects of the drugs on blood pressure were determined. Plasma concentrations of drugs were measured by HPLC, and PK/PD modeling performed by applied biophase model, plasma drug concentrations were linked to the observed systolic blood pressure (SBP) and diastolic blood pressure (DBP) via an effect compartment. The model parameters were estimated using the ADAPT II program. In PK/PD analysis, it was observed the time delay between plasma concentration and effect and the time delay between SBP and DBP. The two time delays were properly explained by PD parameter "K ( eo )" in applied biophase model. As conclusion, the biophase PK/PD model described the relationship between the plasma concentrations of the drugs and the cardiovascular effects, including the time delay between systolic blood pressure and diastolic blood pressure.
Biopharm Drug Dispos. 2008 Jun 12;
Peccinini RG, Ximenes VF, Cesarino EJ, Lanchote VL
An enantioselective high-performance liquid chromatographic method for the analysis of carvedilol in plasma and urine was developed and validated using (-)-menthyl chloroformate (MCF) as a derivatizing reagent. Chloroform was used for extraction, and analysis was performed by HPLC on a C18 column with a fluorescence detector. The quantitation limit was 0.25 ng/ml for S(-)-carvedilol in plasma and 0.5 ng/ml for R(+)-carvedilol in plasma and for both enantiomers in urine. The method was applied to the study of enantioselectivity in the pharmacokinetics of carvedilol administered in a multiple dose regimen (25 mg/12 h) to a hypertensive elderly female patient. The data obtained demonstrated highest plasma levels for the R(+)-carvedilol (AUC(SS) (0-12) 75.64 vs 37.29 ng/ml). The enantiomeric ratio R(+)/S(-) was 2.03 for plasma and 1.49 for urine (Ae(0-12) 17.4 vs 11.7 microg). Copyright (c) 2008 John Wiley & Sons, Ltd.