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At least 19 recordsLinked to original sources
PubMed1992

High-performance liquid chromatographic determination of sotalol in plasma. I. Application to the disposition of sotalol enantiomers in humans.

Two high-performance liquid chromatographic analytical methods have been developed for the measurement of dl-sotalol or d-sotalol and l-sotalol in plasma, using dl-atenolol as internal standard. Quantitation of dl-sotalol was carried out, following solid-phase extraction, on a 5-microns C18 reversed-phase column, with a mobile phase containing acetonitrile, ion-pairing reagent and distilled water, using ultraviolet detection at 235 nm. Quantitation of d-sotalol and l-sotalol was based on derivatisation with the chiral agent S-(-)-alpha-methylbenzyl isocyanate, followed by chromatographic separation on a 3-microns C18 reversed-phase column, with a mobile phase containing methanol, glacial acetic acid and distilled water, with fluorimetric detection at 220 nm excitation and 300 nm emission. A preliminary application of the latter method suggests that the disposition of sotalol in humans is not enantioselective.

Aged↗
PubMed1992

The advantage of d-sotalol over dl-sotalol in a patient with ventricular arrhythmias and comorbid bronchospasm.

The anti-arrhythmic agent sotalol, a racemic mixture of d- and l-isomers, has inherent beta-adrenoceptor blocking activity due to the l-isomer form. For patients with contraindications to beta-adrenoreceptor blockade, dl-sotalol has potentially untoward effects that may limit its usefulness. The case of a man with resistant life-threatening ventricular arrhythmias who responded favorably to dl-sotalol, but developed worsening of underlying bronchospastic lung disease, is presented. A change in therapy to the d-isomer form of sotalol, d-sotalol, was effective in suppressing his ventricular arrhythmias without further aggravation of bronchospasm.

Bronchial Spasm↗
PubMed1992

[Sotalol in the Wolff-Parkinson-White syndrome: an electrophysiological and clinical study].

Distinctly different from the other beta-blocking agents, sotalol prolongs action potential duration in myocardial and Purkinje fibers, and increases atrial as well as ventricular effective refractory periods. Similarly, antegrade and retrograde accessory pathway refractory periods are increased by sotalol. The electrophysiologic and clinical effects of sotalol were studied in 40 patients (31 male and 9 female, mean age 32 +/- 14 years) with Wolff-Parkinson-White Syndrome (WPW). All patients had disabling episodes of supraventricular tachyarrhythmias (ST). Of the 40 patients, 15 (37%) had spontaneous recurrence of paroxysmal supraventricular reciprocating tachycardia (PSRT), 14 (35%) of atrial fibrillation (AF) and 11 (28%) of both PSRT and AF. All of the patients were non responders to serial transesophageal electropharmacological tests using I C class drugs. Sotalol 252 +/- 73 mg daily was administered, and, in steady-state, a new transesophageal study (TS) was performed to observe the re-induction of PSRT and/or AF. 34 patients (85%) were responders to TS (noninducibility of ST, or nonsustained ST or AF inducibility with an increase of 30% in the minimum R-R interval between pre-excitated beats during AF) and the results were confirmed during a follow-up of 17 +/- 9 months. In the non-responder group (5 patients), a I C class drug was associated with sotalol. One patient, who was a "non responder" to sotalol, sotalol + I C class drug, and to amiodarone, underwent surgical therapy. In the 26 patients (65%) who had episodes of PSRT (37%) or episodes of PSRT and AF (28%), it was impossible to reinduce PSRT in 85% of the cases. AF was induced at baseline in all of the studied patients, but after sotalol administration in 15 patients, it was impossible to reinduce AF. The rate of induced AF decreased from 208 +/- 39 beats/min to 156 +/- 36 beats/min (p < 0.001). The mean shortest R-R interval between pre-excitated beats increased from 214 +/- 35 (baseline) to 293 +/- 97 msec (sotalol steady state) (p < 0.001). No side effects were observed. A significant prolongation (p < 0.001) of the QTc interval was observed in all the patients after sotalol administration (from 0.39 +/- 0.2 to 0.42 +/- 0.02 sec.). On the basis of our results, we may conclude that sotalol has a potent effect on the antegrade refractoriness of the anomalous pathway and, in WPW syndrome at risk, is also effective in patients who don't respond to I C class drugs.

Adult↗
PubMed1976

Observations on the efficacy and pharmacokinetics of sotalol after oral administration.

The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 - 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subject. The half-life of sotalol in plasma was 12.7 +/- SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of beta-adrenoceptors.

Administration, Oral↗
PubMed1992

Effects of sotalol on the signal-averaged electrocardiogram in patients with sustained ventricular tachycardia: relation to suppression of inducibility and changes in tachycardia cycle length.

OBJECTIVES: This study examines the effects of sotalol on the signal-averaged electrocardiogram (ECG) in patients with spontaneous and inducible sustained ventricular tachycardia and correlates these findings with the effect of sotalol on tachycardia inducibility and tachycardia rate. BACKGROUND: Standard electrocardiography generally does not detect any change in the duration of the QRS complex resulting from sotalol therapy. However, the signal-averaged ECG is more sensitive than the standard ECG for detecting changes in QRS duration induced by antiarrhythmic drugs and can also detect changes in late potential duration. METHODS: Signal-averaged electrocardiography was performed before therapy in 30 patients with spontaneous and inducible ventricular tachycardia, and both electrophysiologic study and a signal-averaged ECG were repeated during therapy with d,l-sotalol. RESULTS: During sotalol therapy the signal-averaged QRS duration decreased by 2.6 +/- 6.6 ms in the 11 patients with no inducible tachycardia during therapy, whereas it increased by 3.8 +/- 5.8 ms (p = 0.01) in the 19 patients with inducible tachycardia during therapy. In the latter group there was a significant positive correlation between prolongation of tachycardia cycle length and prolongation of late potential duration by sotalol (r = 0.56, p = 0.01). CONCLUSIONS: Sotalol can alter QRS and late potential duration as measured by the signal-averaged ECG. Prolongation of QRS duration or late potential duration may reflect a slowing of conduction by sotalol that may interfere with this agent's antiarrhythmic efficacy and slow ventricular tachycardia.

Capsules↗
PubMed1992

Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia.

In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation.

Bradycardia↗
PubMed1992

Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality.

OBJECTIVE: A comparison of the efficacy of verapamil, sotalol, and flecainide to suppress right ventricular tachycardia (VT) in patients with a clinically normal heart. DESIGN: Patients underwent treatment serially with verapamil (360 mg daily), sotalol (240 or 320 mg daily), and flecainide (200 or 300 mg daily), (the larger dose was for patients heavier than 80 kg) to suppress tachycardia. Each drug was given orally for five half lives before testing. PATIENTS: 23 patients with right VT associated with a clinically normal heart were studied. OUTCOME MEASURES: The effects of drug treatment were examined by the number of ventricular events on 24 hour Holter monitoring, and the ability of tachycardia to be induced by treadmill exercise testing (Bruce protocol) and programmed ventricular stimulation (Wellens protocol), compared with drug free baseline tests. SETTING: Patients were studied in a tertiary referral centre. RESULTS: All three drugs suppressed ventricular salvos (> 3, < 5 consecutive ventricular premature contractions) (p < 0.01) and VT (p < 0.05) on Holter monitoring and did not differ statistically in effect. Exercise induced VT was also suppressed by all three drugs (p < 0.01), and of these sotalol was the most effective although this was not statistically significant (14/23 inducible when drug free, 4/23 on flecainide, 2/23 on sotalol, 5/23 on verapamil). Sustained and non-sustained VT induced by programmed stimulation was also suppressed by the three drugs (p < 0.01) and again sotalol was the best of these though the differences did not achieve statistical significance (17/23 inducible when drug free, 4/17 on flecainide, 2/17 on sotalol, and 6/17 on verapamil). Proarrhythmic effects of drugs were found in a few patients. There was no difference in the efficacy of the drugs in patients with histological abnormalities of the myocardium when compared with those of normal histology. CONCLUSIONS: Ventricular tachycardia associated with a clinically normal heart can be suppressed by flecainide, sotalol, or verapamil. In individual patients sotalol was the most frequently effective drug (effective in > 89% of patients) and is a suitable choice for first line treatment.

Adult↗
PubMedDate not supplied

A new beta adrenergic blocking agent, sotalol, in the treatment of angina pectoris. A double blind-crossed treatment study.

The present therapy for coronary insufficiency includes the use of drugs which decrease the cardiac work, thus reducing the needs for oxygen (beta adrenergic blocking agents). The 4- (2-isopropylamino-1-hydroxyethil) methane sulfonamylide (Sotalol (R)) is considered the most active of the alkylsulfonamide phethenolamines group. 69 patients with angina pectoris were selected for treatment with Sotalol. The administration was preceded by a five weeks period during which the patients received placebo. Afterwards they received for three weeks a dose of Sotalol (titration period), set the optimal effective dose. At the end of this period all patients began a double blind-crossed treatment which continued for 12 weeks. Two schedules were followed: group 1, Sotalol-placebo; group 2, placebo-Sotalol. No statistically significant variations were shown in the number of anginose attacks during the initial placebo period. The decline in the number of anginose attacks during the titration period (Group 1: weeks 5 to 8, p less than 0.0001; Group 2: weeks 5 to 8, p less than 0.0002) is statistically significant. In the first group the continued administration of Sotalol decreased the number of painful attacks even further, which describe a slope which is abruptly interrupted at the end of the six weeks, coinciding with the initiation of the placebo treatment (Group 1: weeks 8 to 14, p less than 0.001, significant). In group 2 (drug-placebo-drug) the administration of the placebo in the six weeks following the titration period was followed by a recrudescence of the symptomatology, whose intensity, however remained far below that recorded during the initial period (Group 2: weeks 8 to 14, p less than 0,0783, not significant). Then, in the final six weeks, the administration of Sotalol produced a sustained and considerable improvement in the weekly number of anginose attacks (Group 2: weeks 14 to 20, p less than 0.0011, significant). All the differences produced by the ingestion of Sotalol are statistically significant. These facts, together with the absence of clinical or humoral side effects incontestably bear out the efficacy of the drug in controlling the number and the intensity of painful attacks of coronary origin.

Adult↗
PubMedDate not supplied

Long-term sotalol therapy in patients with arrhythmias.

Sotalol is a pure beta-adrenergic receptor antagonist. The present study was divided into a first and second therapy period. A total of 38 patients with atrial or ventricular arrhythmias were included in the first therapy period. After a drug-free period of approximately two months, 14 of the 38 patients entered the second therapy period and were given oral sotalol. During the two treatment periods, oral sotalol was given in doses ranging from 40 to 480 mg/day for 0.5 to 11 months in the first period and for four to nine months in the second period. Oral sotalol decreased or abolished arrhythmias in 92 per cent of the patients in the first therapy period and in all the patients in the second therapy period. Minor side effects occurred in two patients. Sotalol possesses a unique class III antiarrhythmic action. The electrophysiological profile is different from other beta-adrenergic blocking agents in that sotalol prolongs the duration of the intracellularly recorded action potential. This property may contribute to the antiarrhythmic efficacy demonstrated with sotalol.

Adult↗
PubMed1992

Effects of ibutilide on spontaneous and induced ventricular arrhythmias in 24-hour canine myocardial infarction: a comparative study with sotalol and encainide.

The electrophysiologic and antiarrhythmic effects of ibutilide, sotalol, and encainide were compared in dogs 24 h after myocardial infarction. Ibutilide (0.03 to 0.3 mg/kg i.v.) prevented the induction of ventricular arrhythmias in 100% of the dogs that had demonstrated inducible ventricular arrhythmias prior to treatment. This antiarrhythmic action was associated with significant increases in ventricular refractoriness and monophasic action potential duration. Sotalol (1.0 to 10.0 mg/kg i.v.) increased the ventricular refractory period and monophasic action potential duration and prevented the induction of ventricular arrhythmias in 75% of the dogs that demonstrated inducible ventricular tachyarrhythmias at baseline. Although 10 mg/kg of sotalol was required to prevent the initiation of ventricular tachycardia, this dose produced marked cardiovascular depression and hypotension in 50% of the dogs tested. Neither ibutilide nor sotalol significantly decreased the incidence of spontaneous ventricular arrhythmias. The class IC agent encainide (0.3 to 3.0 mg/kg i.v.) was successful in preventing the induction of ventricular arrhythmias in only 20% of the dogs tested. However, in contrast to ibutilide and sotalol, encainide significantly reduced spontaneous arrhythmias. Atrial and ventricular refractoriness were significantly increased only after the highest dose of encainide tested (3.0 mg/kg). Over the dose ranges studied, the relative efficacy for prevention of pacing-induced ventricular arrhythmias was ibutilide greater than sotalol much greater than encainide. For suppression of spontaneous ventricular arrhythmias, the relative efficacy was encainide much greater than ibutilide = sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Thrice-daily blood pressure readings on sotalol in the treatment of hypertension: once- versus twice-daily regimen.

Thirty patients with mild to severe essential hypertension satisfactorily controlled by twice-daily sotalol therapy entered a double-blind, crossover study comparing the efficacy, tolerability, and safety of their usual twice-daily sotalol administration with the same dosage given once daily. Each double-blind period extended eight weeks, during which blood pressure and pulse rate were recorded by a nurse three times daily on alternate days during the last week of each period in the patients' usual living conditions. Plasma sotalol concentration was measured before the morning dosage of sotalol. No statistically significant differences in the parameters were found between once- and twice-daily sotalol administration using sotalol in daily dosages from 80 to 320 mg. All patients concluded the trial, and no increase in side effects was noted during the once-daily period.

Adult↗
PubMed1976

A comparison of the beta-blocking activities of practolol, sotalol, and propranolol in human and guinea pig tracheal smooth muscle.

Beta adrenergic blockade was studied in vitro with human tracheal muscle strips and guinea pig tracheal chains. It was shown in isolated smooth muscle from both man and guinea pig that the order of potency for the three beta-blocking agents studied was: propranolol greater than sotalol greater than practolol. Under the conditions of this study, propranolol was about 30,000 times and sotalol about 30 times as potent as practolol. The order of potency suggests that the nature of adrenergic blockade induced by practolol on tracheal smooth muscle is only weakly beta2-relative to the blocking effects of propranolol and sotalol. Beta adrenergic blockade by propranolol, sotalol, and practolol produced different degrees of increased histamine lethality in mice. Whereas both propranolol at 0.01 mg/kg and sotalol at 1.0 mg/kg resulted in 100% histamine-induced lethality, practolol at 50 mg/kg resulted in only 50% histamine-induced lethality. These data, when added to those from our previous studies, suggest that the mechanisms responsible for resistance to the effects of histamine in untreated mice are at least partially mediated by the beta2-adrenergic system. Thus, in three different tissues, the blocking activity of practolol was shown to be less than that of sotalol or propranolol.

Animals↗
PubMed1992

Prediction of sotalol-induced maximum steady-state QTc prolongation from single-dose administration in healthy volunteers.

The relationship between racemic sotalol plasma concentrations and QTc interval prolongation after both single-dose and repeated administration of three sotalol oral doses was studied in a randomized crossover protocol performed in 10 healthy volunteers. QTc interval increase was significant after the three single-dose sotalol administrations and was significantly related to the administered dose (p < 0.0001). In 21 of 30 analyses, QTc interval was linearly correlated with sotalol plasma concentrations. After the 320 mg dose, the linear model was a best fit for 90% of the cases, and no hysteresis was observed. After repeated sotalol administration, 69 of 87 QTc interval measurements at steady state could be predicted from the plasma concentration versus effect relationship established after single-dose 320 mg administration. Seventeen of 18 errors (94%) corresponded to QTc intervals that were significantly lower than predicted. These findings suggest that a short-term individual linear model determined after a 320 mg test dose of sotalol allows a good prediction of expected maximal increase in QTc duration in healthy subjects.

Administration, Oral↗
PubMed1992

Differential effects of the new class III antiarrhythmic agents almokalant, E-4031 and D-sotalol, and of quinidine, on delayed rectifier currents in guinea pig ventricular myocytes.

OBJECTIVES: The effects of almokalant (4-[3-ethyl[3-(propylsulphinyl)propyl]-amino]-2-hydroxy-propoxy]- benzonitrile), E-4031 (1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4-methylsulphonyl-amino- benzoyl)piperidine), d-sotalol, and quinidine were investigated on the delayed K+ rectifier current IK. The aim of the study was to compare the drug action on the two components of this current. METHODS: Membrane currents were measured in ventricular myocytes from guinea pig hearts with the whole cell voltage clamp technique. IK was activated during clamp steps from a holding potential of -40 mV to test potentials -30 and +50 mV. The tail current Itail was measured upon stepping back to holding potential. RESULTS: In control experiments. IK and Itail declined spontaneously ("run down"). With 300 ms long test pulses to +50 mV, only d-sotalol (10(-4) M) caused a significant further decrease in IK, whereas all four agents significantly reduced Itail (almokalant 10(-6) M, E-4031 10(-7) M, quinidine 10(-5) M). When tested with 1 s long clamp steps at various potentials almokalant (3 x 10(-6) M), E-4031 (10(-6) M), quinidine (10(-5) M), and d-sotalol (10(-4) M) reduced IK in the potential range between -20 and +40 mV, yielding a bell shaped inward rectifying drug sensitive current. Itail was reduced by almokalant and E-4031 over the whole voltage range with saturation of block positive to +20 mV. Similar reductions with quinidine but not with d-sotalol were also significant. With rest pulses to +50 mV of increasing duration (25 ms-4000 ms), Itail developed with a faster time course than IK and therefore the ratio of Itail/IK declined with pulse duration. With almokalant and E-4031, this ratio became independent of test pulse duration. For 250 ms pulses, Itail/IK was also significantly reduced by d-sotalol and quinidine. CONCLUSION: Inhibition of the rapidly activating inwardly rectifying component of IK is prominent with almokalant and E-4031 and less pronounced with d-sotalol and quinidine. Since inhibition of this component prolongs the cardiac action potential, it should contribute to the antiarrhythmic properties of the agents.

Action Potentials↗
PubMed1975

Serum levels and half-life of sotalol in chronic renal failure.

The elimination of sotalol was studied in 25 patients with chronic renal failure. All patients were given a single 160 mg dose of sotalol orally and their sotalol serum levels were determined after 4, 6, 8, 10 and 12 hours. The elmination of sotalol was distinctly slower as the serum creatinine concentration rose. The half-lives, calculated graphically, were in lenear ratio to the serum creatinine values (r = 0,91; p less than 0.001). In accordance with the results, it is probable that sotalol accumulates in chronic renal insufficiency. Since beta-blockers may impair renal function, even in therapeutic concentrations, the dosage of sotalol, in particular, must be reduced in patient with kidney disease.

Administration, Oral↗
PubMed1977

[Studies on the pharmacokinetics and effects of beta-adrenergic blocking agents, sotalol (author's transl)].

Present investigation was undertaken to elucidate what pharmacokinetic parameters in animal experiment could be of more predictable for human clinical trial of beta-blocking agents. Sotalol was administered as a model drug to dogs, rats, and men. Dog experiments disclosed that the apparent volume of distribution of sotalol was about 4 times larger than the space of total body water and the plasma level of sotalol was 1.0-2.0 and 2.3-3.4 microgram/ml when the beta-blocking index showed 50 and 100% to the intravenous bolus injection of isoproterenol (0.1-1.0 microgram/kg). The clearance studies of dogs and men suggested that the elimination of sotalol depended essentially on renal excretion. The regression coefficient of beta-blocking index and plasma level of this agent in dog experiment using 0.1 microgram/kg isoproterenol was nearly equal to that of human study in which maximal exercise test was performed. Rat experiments showed a large apparent volume of distribution as well as in human study and high concentrations of sotalol in various tissues of rats. The plasma level of sotalol was well correlated with the content of the drug in such organs as heart, lung, liver, and kidneys.

Administration, Oral↗
PubMedDate not supplied

Effects of the beta-adrenoceptor blocking agent sotalol on CNS: sleep, EEG, and psychophysiological parameters.

Sotalol (Sotalex), 320 or 960 mg, was administered to 12 healthy subjects daily for a period of four days in a double-blind trial over 11 days. The effects of sotalol on heart rate, blood pressure, EEG, subjective quality of sleep, polygraphically determined sleep pattern, and psychophysiological parameters such as psychomotor performance, memory, perception, vigilance, and general condition were studied and were related to dosage and plasma levels. Steady-state plasma levels of sotalol were reached within 24 hours after a single dose; 960 mg resulted in plasma levels three times higher than those reached with 320 mg, which indicates first-order linear absorption. The effects of sotalol on EEG, sleep, and performance in psychological tests were equivocal and do not yield evidence for CNS activity of sotalol.

Adolescent↗