Pharmacology, pharmacodynamics and pharmacokinetics of sotalol

Antonaccio, Michael J.; Gomoll, Allen W.

doi:10.1016/0002-9149(90)90196-8

Cited by 79 publications

(33 citation statements)

References 31 publications

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“…Based on these studies, an intravenous regimen for the replacement of 80 mg oral therapy requires 75 mg intravenous sotalol administered as a 5-hour infusion. Since the pharmacokinetics of sotalol are linear and dose proportional [2,3,4,15,16,17], 150 mg intravenous sotalol administered over 5 h will provide a similar C max and AUC as 160 mg oral sotalol.…”

Section: Discussionmentioning

confidence: 99%

“…Using the equation for sotalol concentration = (QTc – 398)/0.0342, the formula yields a sotalol concentration of 1,520 ng/ml [1,520 = (450–398)/0.0342]. Due to the linear pharmacokinetics of sotalol, doubling the sotalol dose would double the maximum and trough sotalol concentrations [2,3,4,15,16,17]. In this case, increasing the sotalol dose (1.5 times) from 80 to 120 mg would increase the sotalol concentration 1.5 times to 2,280 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

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QT Prolongation and Serum Sotalol Concentration Are Highly Correlated following Intravenous and Oral Sotalol

Somberg

Preston

Ranade³

et al. 2010

Cardiology

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Objectives: The aim of this study was to evaluate the correlation between QT interval (QT) and serum sotalol concentration following a single low dose of oral and intravenous sotalol. Methods: Fifteen healthy volunteers received 75 mg intravenous sotalol over 2.5 h and 80 mg oral sotalol in a random order. Serum sotalol concentrations and 12-lead electrocardiograms were obtained simultaneously at baseline and 7 times following dosings. Rate-corrected QT (QTc) was calculated by the Bazett, Fridericia and Framingham formulas. Linear regression analysis was performed between sotalol concentrations and QT measurements. Results: Significant QT prolongation was seen at very low sotalol doses and serum concentrations. QTc intervals calculated by the Framingham and Fridericia formulas showed the strongest and virtually identical correlations with serum sotalol concentration (r ≧ 0.97, p < 0.001) following oral and intravenous administrations. The equation QTc = 0.0342 (sotalol concentration) + 398 closely predicted actual QTc at any sotalol concentration. Conclusions: A strong correlation was observed between serum sotalol concentration and QTc prolongation across the entire concentration range. Low-dose sotalol caused significant QT prolongation. At similar concentrations, intravenous and oral sotalol caused similar QT and QTc effects. Knowing the QT effect can be used to guide further dose increase.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

QT Prolongation and Serum Sotalol Concentration Are Highly Correlated following Intravenous and Oral Sotalol

Somberg

Preston

Ranade³

et al. 2010

Cardiology

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“…As previously mentioned, dl-sotalol causes a reduction in HR associated with the class III action plasma-concentration-dependently (34,35,37,38). It is also known that more than 80% of an oral dose of dlsotalol is absorbed (29) and dl-sotalol is not metabolized and only weakly bound to plasma proteins (30 -35).…”

Section: Effect Of Dl-sotalolmentioning

confidence: 99%

QT PRODACT: Inter-facility Variability in Electrocardiographic and Hemodynamic Parameters in Conscious Dogs and Monkeys

Sasaki

Shimizu²,

Suganami

et al. 2005

J Pharmacol Sci

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Abstract. In safety pharmacology studies, the effect of a test compound on the electrocardiogram is routinely examined by using conscious dogs. However, the results may be widely variable. The monkey, on the other hand, has scarcely been used for such studies; and as yet, there have not been reported studies on monkeys conducted at several facilities with a standard protocol. In the present study, we examined inter-facility variabilities in electrocardiographic and hemodynamic parameters as described below. We analyzed the data from 8 facilities (9 test groups) on dogs and 5 facilities (7 test groups) on monkeys. This data was obtained from the studies employing the following standard protocol: dl-Sotalol or a vehicle (0.5 w / v% methylcellulose solution) was given to animals; and the PR interval, QRS duration, QT interval, heart rate, and mean blood pressure were determined time-sequentially before and after administration of the vehicle or dl-sotalol in each test group. dl-Sotalol produced a prolongation of the maximum mean QTcF interval in conscious dogs and QTcB interval in conscious monkeys by more than 10% in every test group. No difference in the corrected QT interval among the test groups was observed in dogs, but a difference was observed in monkeys. Supplementary material (Appendix): available only at http://dx

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“…Since the currently known effects of class III antiarrhythmics [17] alone cannot fully explain the defibrillating ability of D-sotalo1, we have assumed that D-sotalol possesses some of the above mentioned antiarrhythmic-defibrillating properties. D-Sotalol exhibits a positive inotropic effect [18], increases cardiac conduction velocity [19], and increases the maximal rate of phase "0" depolarization (Vmax) [20], intercellular coupling [21], and intracellular cAMP concentration [22,23]. Therefore, the aim of this study was to elucidate whether pretreatment with D-sotalol prevented the deteriorating (intercellular tmcoupling) effect of hypoxia.…”

Section: Introductionmentioning

confidence: 99%

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

1996

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The effects of D-sotalol on intercellular electrical coupling and ultrastructure under hypoxic conditions were investigated in myocardial samples from eight young (1-2 months) and four older (10-12 months) guinea pigs. A right ventricular muscle strip was kept simultaneously in two divided chambers and superfused with normoxic and/or hypoxic (97% N2+ 3% Co2) Krebs solution. Hypoxia caused shortening of action potential duration (APD) and electrical cell-to-cell uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30 min), administration of 3.10(-7)M of D-sotalol to the hypoxic perfusate led to a recovery of electrical coupling. Transmission electron microscopy revealed moderate reversible ultrastructural alterations of the cardiomyocytes. No apparent changes in intercellular junctions were observed. The recoupling effect of sotalol decreased with the time of hypoxia as the ultrastructural damage progressed. After prolonged hypoxia (more than 30 min), cardiomyocytes were markedly injured, intercellular junctions were severely affected, and gap junctions occurred less frequently. In these cases, administration of D-sotalol caused only transient recoupling. After 1 h of hypoxia, no recoupling was observed. Pretreatment with D-sotalol prevented hypoxia-induced electrical uncoupling and markedly attenuated ultrastructural damage, although shortening of APD still persisted. Our results indicate that the cardioprotective effect of D-sotalol on electrical intercellular coupling is closely associated with sotalol-induced prevention of the ultrastructural damage. Considering previous results, we suggest that this protective effect of D-sotalol may be related to its ability to increase intracellular cyclic adenosine monophosphate and, thereby, to decrease cytosolic free Ca. These effects can explain the antiarrhythmic and defibrillating properties of D-sotalol.

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Pharmacology, pharmacodynamics and pharmacokinetics of sotalol

Cited by 79 publications

References 31 publications

QT Prolongation and Serum Sotalol Concentration Are Highly Correlated following Intravenous and Oral Sotalol

QT Prolongation and Serum Sotalol Concentration Are Highly Correlated following Intravenous and Oral Sotalol

QT PRODACT: Inter-facility Variability in Electrocardiographic and Hemodynamic Parameters in Conscious Dogs and Monkeys

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

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