-
Analytical Sciences : the International... 2017In order to overcome deficiencies for simultaneously determining felodipine (FDP) and metoprolol (MPL) with low recovery and low sensitivity, a new online SPE coupled...
In order to overcome deficiencies for simultaneously determining felodipine (FDP) and metoprolol (MPL) with low recovery and low sensitivity, a new online SPE coupled with the liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method for the simultaneous quantitative determination of FDP and MPL in beagle dog plasma was established. The SPE extraction of FDP and MPL was performed on a Retain PEP Javelin column (10 × 2.1 mm, 5 μm), while the chromatographic separation was achieved on a ZORBAX SB-C18 (50 × 2.1 mm, 3.5 μm) analytical column. Multiple reaction monitoring operated in the positive ion mode was adopted in MS detection, and the precursors to the product ion transition values of m/z 384/338.1, 268/74.2 and 436.2/207.1 were used to measure FDP, MPL and the internal standard (valsartan). The high throughput, accurate and sensitive method for FDP and MPL was validated and applied to the bioavailability research of FDP and MPL in beagle dogs.
Topics: Animals; Chromatography, Liquid; Dogs; Felodipine; Internet; Male; Metoprolol; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 28690250
DOI: 10.2116/analsci.33.755 -
Journal of Hypertension Apr 2017The objective of this article is to compare blood pressure (BP)-lowing effects of nitrendipine and hydrochlorothiazide and nitrendipine and metoprolol, and estimate the... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
The objective of this article is to compare blood pressure (BP)-lowing effects of nitrendipine and hydrochlorothiazide and nitrendipine and metoprolol, and estimate the economic effect of these therapies on hypertension.
METHODS
Outpatients (N = 793) 18-70 years of age with stage 2 or severe hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg) were recruited from four randomly selected rural community health centers in Beijing and Jilin. After drug wash out, they were randomly divided into nitrendipine and hydrochlorothiazide group or nitrendipine and metoprolol group. The costs of drug treatment for hypertension were calculated and general estimation, whereas effectiveness was measured as a reduction in SBP and DBP at the end of a 24-week study period.
RESULTS
Overall, 623 patients were eligible for the study and after a 24-week follow-up, SBP and DBP were 131.2/82.2 mmHg for the nitrendipine and hydrochlorothiazide group and 131.4/82.9 mmHg for the nitrendipine and metoprolol group and these were not significantly different (P = 0.7974 SBP and P = 0.1166 DBP). Comparing with nitrendipine and metoprolol, the cost of nitrendipine and hydrochlorothiazide was less, and its effectiveness was similar. The cost/effect ratio (US$/mmHg) was 1.4 for SBP and 2.8 for DBP for the nitrendipine and hydrochlorothiazide group, and 1.9 and 3.8 for the nitrendipine and metoprolol group's SBP and DBP values, respectively. The incremental cost per patient for achieving target BP was 5.1. Adverse events were mild or moderate and there were no differences between treatment groups.
CONCLUSION
Treating hypertension with nitrendipine and hydrochlorothiazide was cost-effective than nitrendipine and metoprolol, and these data will allow more reasonable and efficient allocation of limited resources in low-income countries.
Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Beijing; Blood Pressure; Community Health Centers; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Health Care Costs; Humans; Hydrochlorothiazide; Hypertension; Male; Metoprolol; Middle Aged; Nitrendipine; Prospective Studies; Rural Health Services; Young Adult
PubMed: 27977472
DOI: 10.1097/HJH.0000000000001209 -
American Journal of Kidney Diseases :... Sep 2018Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite... (Comparative Study)
Comparative Study Observational Study
BACKGROUND
Carvedilol and metoprolol are the β-blockers most commonly prescribed to US hemodialysis patients, accounting for ∼80% of β-blocker prescriptions. Despite well-established pharmacologic and pharmacokinetic differences between the 2 medications, little is known about their relative safety and efficacy in the hemodialysis population.
STUDY DESIGN
A retrospective cohort study using a new-user design.
SETTING & PARTICIPANTS
Medicare-enrolled hemodialysis patients treated at a large US dialysis organization who initiated carvedilol or metoprolol therapy from January 1, 2007, through December 30, 2012.
PREDICTOR
Carvedilol versus metoprolol initiation.
OUTCOMES
All-cause mortality, cardiovascular mortality, and intradialytic hypotension (systolic blood pressure decrease ≥ 20mmHg during hemodialysis plus intradialytic saline solution administration) during a 1-year follow-up period.
MEASUREMENTS
Survival models were used to estimate HRs and 95% CIs in mortality analyses. Poisson regression was used to estimate incidence rate ratios (IRRs) and 95% CIs in intradialytic hypotension analyses. Inverse probability of treatment weighting was used to adjust for several demographic, clinical, laboratory, and dialysis treatment covariates in all analyses.
RESULTS
27,064 individuals receiving maintenance hemodialysis were included: 9,558 (35.3%) carvedilol initiators and 17,506 (64.7%) metoprolol initiators. Carvedilol (vs metoprolol) initiation was associated with greater all-cause (adjusted HR, 1.08; 95% CI, 1.02-1.16) and cardiovascular mortality (adjusted HR, 1.18; 95% CI, 1.08-1.29). In subgroup analyses, similar associations were observed among patients with hypertension, atrial fibrillation, heart failure, and a recent myocardial infarction, the main cardiovascular indications for β-blocker therapy. During follow-up, carvedilol (vs metoprolol) initiators had a higher rate of intradialytic hypotension (adjusted IRR, 1.10; 95% CI, 1.09-1.11).
LIMITATIONS
Residual confounding may exist.
CONCLUSIONS
Relative to metoprolol initiation, carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality. One potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.
Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Carvedilol; Cohort Studies; Female; Humans; Male; Metoprolol; Middle Aged; Mortality; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Time Factors
PubMed: 29653770
DOI: 10.1053/j.ajkd.2018.02.350 -
Annals of Cardiac Anaesthesia 2023Ivabradine is a specific heart rate (HR)-lowering agent which blocks the cardiac pacemaker I channels. It reduces the HR without causing a negative inotropic or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ivabradine is a specific heart rate (HR)-lowering agent which blocks the cardiac pacemaker I channels. It reduces the HR without causing a negative inotropic or lusitropic effect, thus preserving ventricular contractility. The authors hypothesized that its usefulness in lowering HR can be utilized in patients undergoing off-pump coronary artery bypass (OPCAB) surgery.
OBJECTIVE
To study the effects of preoperative ivabradine on hemodynamics (during surgery) in patients undergoing elective OPCAB surgery.
METHODS
Fifty patients, New York Heart Association (NYHA) class I and II, were randomized into group I (control, n = 25) and group II (ivabradine group, n = 25). In group I, patients received the usual anti-anginal medications in the preoperative period, as per the institutional protocol. In group II, patients received ivabradine 5 mg twice daily for 3 days before surgery, in addition to the usual anti-anginal medications. Anesthesia was induced with fentanyl, thiopentone sodium, and pancuronium bromide as a muscle relaxant and maintained with fentanyl, midazolam, pancuronium bromide, and isoflurane. The hemodynamic parameters [HR and mean arterial pressure (MAP)] and pulmonary artery (PA) catheter-derived data were recorded at the baseline (before induction), 3 min after the induction of anesthesia at 1 min and 3 min after intubation and at 5 min and 30 min after protamine administration. Intraoperatively, hemodynamic data (HR and MAP) were recorded every 10 min, except during distal anastomosis of the coronary arteries when it was recorded every 5 min. Post-operatively, at 24 hours, the levels of troponin T and brain natriuretic peptide (BNP) were measured. This trial's CTRI registration number is CTRI/005858.
RESULTS
The HR in group II was lower when compared to group I (range 59.6-72.4 beats/min and 65.8-80.2 beats/min, respectively) throughout the study period. MAP was comparable [range (78.5-87.8 mm Hg) vs. (78.9-88.5 mm Hg) in group II vs. group I, respectively] throughout the study period. Intraoperatively, 5 patients received metoprolol in group I to control the HR, whereas none of the patients in group II required metoprolol. The incidence of preoperative bradycardia (HR <60 beats/min) was higher in group II (20%) vs. group I (8%). There was no difference in both the groups in terms of troponin T and BNP level after 24 hours, time to extubation, requirement of inotropes, incidence of arrhythmias, in-hospital morbidity, and 30-day mortality.
CONCLUSION
Ivabradine can be safely used along with other anti-anginal agents during the preoperative period in patients undergoing OPCAB surgery. It helps to maintain a lower HR during surgery and reduces the need for beta-blockers in the intraoperative period, a desirable and beneficial effect in situations where the use of beta-blockers may be potentially harmful. Further studies are needed to evaluate the beneficial effects of perioperative Ivabradine in patients with moderate-to-severe left ventricular dysfunction.
Topics: Humans; Ivabradine; Metoprolol; Pancuronium; Troponin T; Hemodynamics; Coronary Artery Bypass, Off-Pump; Fentanyl
PubMed: 37470523
DOI: 10.4103/aca.aca_97_22 -
Journal of the American College of... May 2018
Topics: Defibrillators, Implantable; Humans; Metoprolol; Physical Exertion; Propranolol
PubMed: 29699617
DOI: 10.1016/j.jacc.2018.02.058 -
European Journal of Pharmaceutical... Jan 2017In the current study, we investigated the metoprolol absorption kinetics of an in-house produced oral sustained-release formulation, matrices manufactured via prilling,... (Comparative Study)
Comparative Study
In the current study, we investigated the metoprolol absorption kinetics of an in-house produced oral sustained-release formulation, matrices manufactured via prilling, and two commercially available formulations, ZOK-ZID (reservoir) and Slow-Lopresor (matrix) in both New Zealand White rabbits and Beagle dogs, using a population pharmacokinetic analysis approach. The aim of this study was to compare the in vivo pharmacokinetic (PK) profiles of different formulations based on metoprolol, a selective adrenergic β-receptor antagonist, in dogs and rabbits and to contrast the observed differences. To that end, metoprolol (50 to 200mg) was administered to 6 Beagle dogs and 6 New Zealand White rabbits as a single intravenous (IV) bolus injection and to 8 dogs and 6 rabbits as an oral modified release formulation. To derive pharmacokinetic parameters from the data, a non-linear mixed-effects model was developed using NONMEM where the contribution of observations below the limit of detection (BDL, below detection limit) to the parameter estimates was taken into account in the parameter estimation procedure. In both species and for the three modified release formulations, different absorption models were tested to describe the PK of metoprolol following oral dosing. In Beagle dogs, plasma concentration-time profiles were best described using a sequential zero- and first-order absorption model. In rabbits though, the absorption phase was best described using a first-order process only. In both species, the reservoir formulation ZOK-ZID was behaving quite similarly. In contrast, the absorption properties of both matrix formulations were rather different between species. This study indicates that the PK of the reservoir formulation is similar in both species, even after accounting for the almost completely missed absorption phase in rabbits. The insights gained further illustrate that rabbits are not very well suited to study the PK of the current matrix formulations in view of their less optimal prolonged release characteristics and the resulting fast decline in metoprolol plasma levels.
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dogs; Metoprolol; Rabbits; Species Specificity
PubMed: 27816630
DOI: 10.1016/j.ejps.2016.10.039 -
Journal of General Internal Medicine Nov 2011
Topics: Adrenergic beta-Antagonists; Aged; Drug Eruptions; Humans; Lichenoid Eruptions; Male; Metoprolol
PubMed: 21614631
DOI: 10.1007/s11606-011-1742-5 -
Journal of Clinical Pharmacology Mar 2011Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used beta-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4-phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate-release (IR) tartrate and extended-release (ER) succinate metoprolol formulations. Ten healthy participants received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol area under the plasma concentration-time curve from time 0 to the 24-hour blood draw (AUC(0-24h)) by 4- and 5-fold, respectively for IR, and 3- and 4-fold, respectively, for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol, and stereoselective metabolism is lost. This could theoretically result in greater beta-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses/drug input rates employed.
Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Cross-Over Studies; Cytochrome P-450 CYP2D6 Inhibitors; Delayed-Action Preparations; Drug Interactions; Enzyme Inhibitors; Humans; Male; Metabolic Clearance Rate; Metoprolol; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Stereoisomerism; Young Adult
PubMed: 20400652
DOI: 10.1177/0091270010365559 -
The American Journal of Cardiology Mar 1993Early studies of acute beta-blocking drug therapy, such as metoprolol and acebutolol, in patients with idiopathic dilated cardiomyopathy (IDC) and survivors of acute... (Review)
Review
Early studies of acute beta-blocking drug therapy, such as metoprolol and acebutolol, in patients with idiopathic dilated cardiomyopathy (IDC) and survivors of acute myocardial infarction were interpreted to have detrimental or, at best, neutral effects on cardiac and clinical hemodynamics. Subsequent trials of longer duration with metoprolol versus placebo in patients with IDC demonstrated an "exceptional response" to beta-blocker therapy in some individuals. Hemodynamics and patient demographic characteristics appear not to predict those patients who may or may not benefit. Controlled trials with newer beta-adrenoceptor modulating drugs--such as xamoterol, bucindolol, and carvedilol--have been equivocal in some situations. Xamoterol has been associated with progressive heart failure and increased sudden cardiac deaths, whereas bucindolol improved clinical heart failure symptoms and testing hemodynamic parameters, as did treatment with carvedilol, in patients with ischemic cardiomyopathy. The success of these agents in patients with congestive heart failure may be in their ability to modulate the excessive myocardial stimulation of the beta-adrenergic nervous system while benefitting the dynamics of the peripheral system.
Topics: Adrenergic beta-Antagonists; Cardiomyopathy, Dilated; Female; Hemodynamics; Humans; Male; Metoprolol; Middle Aged
PubMed: 8096675
DOI: 10.1016/0002-9149(93)90086-r -
Vascular Health and Risk Management 2007Beta-blockers have been shown to improve survival in patients with chronic heart failure. The effect of different generations of beta blockers has been debated. Both... (Review)
Review
Beta-blockers have been shown to improve survival in patients with chronic heart failure. The effect of different generations of beta blockers has been debated. Both metoprolol and carvedilol have demonstrated beneficial effects in placebo-controlled trials. In The Carvedilol Or Metoprolol European Trial (COMET) two beta blockers were compared in a double-blind randomized matter. This is the first direct comparison between metoprolol and carvedilol of long-term effect on survival in patients with chronic heart failure. The all-cause mortality was significantly reduced in the favour of carvedilol. The dose and formulation of metoprolol used in this trial has caused debate, and it has been questioned whether a similar beta1-blockade is obtained in the two intervention groups. At this time there is an unresolved debate as to whether carvedilol is a superior beta-blocker or whether differences in beta1-blockade explained the results of COMET.
Topics: Adrenergic beta-Antagonists; Carbazoles; Carvedilol; Europe; Heart Failure; Humans; Metoprolol; Propanolamines; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17583173
DOI: No ID Found