Interaction between sotalol and an antacid preparation

Abstract

Aims: The aim of the study was to investigate the pharmacokinetic interaction between sotalol and antacids, and its pharmacodynamic relevance. Methods: In a randomized cross-over design with three treatment groups, six healthy volunteers received orally either 160 mg of sotalol alone (phase 1), or 160 mg sotalol plus 20 ml of a suspension of an antacid (MAH; magnesium hydroxide (1200 mg) and aluminium oxide (1800 mg) (phase 2) or 160 mg sotalol plus the antacid given 2 h after sotalol administration (phase 3). Heart rate and plasma sotalol concentrations were measured before and 1, 2, 3, 4, 6, 8, 12 and 24 h after sotalol administration. Urinary sotalol excretion was measured for 24 h after sotalol application. Results: C(max) of sotalol decreased from 1.22 ± 0.22 mg l-1 (phase 1) to 0.89 ± 0.29 mg l-1 (phase 2) and increased again to 1.27 ± 0.18 mg l-1 in phase 3. A similar significant change was noted in AUC (15.6 ± 2.75 mg l-1, 12.3 ± 3.04 mg h l-1 and 15.0 ± 2.06 mg l-1) and in the amount of cumulative urinary excretion (79.2 ± 11.1 mg, 72.1 ± 11.2 mg and 80.6 ± 7.9 mg), respectively. t(max) and elimination half-life (t( 1/4 ,z) of sotalol remained unchanged in the presence of MAH. After combined administration with MAH, the area under the heart rate curve of sotalol was reduced between 0 and 4 h when compared across treatments. Conclusions: Combined administration of sotalol and MAH decreased the serum sotalol levels. The interaction can be avoided by a two hour interval between application of these drugs.