Sotalol

D,l-sotalol is a non-selective hydrophilic β-adrenergic receptor blocking agent, devoid of intrinsic sympathomimetic activity or membrane stabilizing activity.

Sotalol has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. Sotalol has no known effect on the upstroke velocity and therefore no effect on the depolarisation phase.

Sotalol uniformly prolongs the action potential duration in cardiac tissues by delaying the repolarisation phase. Its major effects are prolongation of the atrial, ventricular and accessory pathway effective refractory periods.

The Class II and III properties may be reflected on the surface electrocardiogram by a lengthening of the PR, QT and QTc (QT corrected for heart rate) intervals with no significant alteration in the QRS duration.

The d- and l-isomers of sotalol have similar Class III antiarrhythmic effects while the l-isomer is responsible for virtually all of the beta-blocking activity. Although significant beta-blockade may occur at oral doses as low as 25 mg, Class III effects are usually seen at daily doses of greater than 160 mg.

Its β-adrenergic blocking activity causes a reduction in heart rate (negative chronotropic effect) and a limited reduction in the force of contraction (negative inotropic effect). These cardiac changes reduce myocardial oxygen consumption and cardiac work. Like other β-blockers, sotalol inhibits renin release. The renin-suppressive effect of sotalol is significant both at rest and during exercise. Like other beta adrenergic blocking agents, sotalol produces a gradual but significant reduction in both systolic and diastolic blood pressures in hypertensive patients. Twenty-four-hour control of blood pressure is maintained both in the supine and upright positions with a single daily dose.

The bioavailability of oral sotalol is essentially complete (greater than 90%). After oral administration, peak levels are reached in 2.5 to 4 hours, and steady-state plasma levels are attained within 2-3 days.

The absorption is reduced by approximately 20% when administered with a standard meal, in comparison to fasting conditions. Over the dosage range 40-640 mg/day sotalol displays dose proportionality with respect to plasma levels.

Distribution occurs to a central (plasma) and a peripheral compartment, with an elimination half-life of 10-20 hours. Sotalol does not bind to plasma proteins and is not metabolised. There is very little inter-subject variability in plasma levels. Sotalol crosses the blood brain barrier poorly, with cerebrospinal fluid concentrations only 10% of those in plasma.

The primary route of elimination is renal excretion. Approximately 80 to 90% of a dose is excreted unchanged in the urine, while the remainder is excreted in the faeces. Lower doses are necessary in conditions of renal impairment.

Age does not significantly alter the pharmacokinetics, although impaired renal function in geriatric patients can decrease the excretion rate, resulting in increased drug accumulation.

No further particulars.