In healthy subjects, the oral bioavailability of BETAPACE® (sotalolhydro chloride) is 90-100%. After oral administration, peak plasma concentrations are reached in 2.5 to 4 hours, and steady-state plasma concentrations are attained within 2-3 days (i.e., after 5-6 doses when administered twice daily). Over the dosage range 160-640 mg/day BETAPACE® (sotalolhydro chloride) displays dose proportionality with respect to plasma concentrations. Distribution occurs to a central (plasma) and to a peripheral compartment, with a mean elimination half-life of 12 hours. Dosing every 12 hours results in trough plasma concentrations which are approximately one-half of those at peak.

BETAPACE® (sotalolhydro chloride) does not bind to plasma proteins and is not metabolized. BETAPACE® (sotalolhydrochloride) shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l enantiomers of sotalolare essentially identical. BETAPACE® (sotalolhydro chloride) crosses the blood brain barrier poorly. Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary in conditions of renal impairment (see DOSAGE AND ADMINISTRATION). Age per se does not significantly alter the pharmacokinetics of BETAPACE®, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation. The absorption of BETAPACE® (sotalolhydro chloride) was reduced by approximately 20% compared to fasting when it was administered with a standard meal. Since BETAPACE® (sotalolhydro chloride) is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of BETAPACE®.

The combined analysis of two unblinded, multicenter trials (a single dose and a multiple dose study) with 59 children, aged between 3 days and 12 years, showed the pharmacokinetics of sotalol to be first order. A daily dose of 30 mg/m 2 of sotalol was administered in the single dose study and daily doses of 30, 90 and 210 mg/m 2 were administered q 8h in the multi-dose study. After rapid absorption with peak levels occurring on average between 2-3 hours following administration, sotalol was eliminated with a mean half life of 9.5 hours. Steady-state was reached after 1-2 days. The average peak to trough concentration ratio was 2. BSA was the most important covariate and more relevant than age for the pharmacokinetics of sotalol. The smallest children (BSA < 0.33m 2 ) exhibited a greater drug exposure (+59%) than the larger children who showed a uniform drug concentration profile. The intersubject variation for oral clearance was 22%.

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