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 1/2,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.

Assessment of the effect of a single oral dose of telithromycin on sotalol‐induced qt interval prolongation in healthy women

“…After single oral administration of 160 mg of sotalol and placebo in healthy female subjects, plasma pharmacokinetics of sotalol was similar to that obtained in previous studies at the same dose [21,22]. In the presence of telithromycin, unexpected modifications of sotalol pharmacokinetics parameters were observed.…”

Informing a Comprehensive Risk Assessment of Infant Drug Exposure From Human Milk: Application of a Physiologically Based Pharmacokinetic Lactation Model for Sotalol

“…For the oral administration, the dissolution parameters (time 50% dissolved, and dissolution shape) and intestinal permeability were optimized with the refine set to 53 minutes, 0.98, and 5.9e‐6 cm/min, respectively. From the test sets, the resulting IV and PO profiles are well described even under new conditions, including IV infusion (2.5 hours 26 ), given with another agent (antacid 30 ) and a new population (Japanese 25 ).…”

“…The remainder of the data were placed in the refinement data set. For the PO adult model building, oral dosing data were collected from 141 total patients, also split into build (n = 33 21,27 ), refine (n = 46 23,28,29 ), and test (n = 62 25,26,30 ) sets. These splits were not even, as the literature data were divided on a per-study basis; however, the internal FDA (n = 41) data were distributed randomly across the three sets (13, 14, and 14 for the build, refine, and test sets, respectively).…”

Drug Interactions Affecting Antiarrhythmic Drug Use

“…Coadministration with food or antacids can slightly decrease plasma sotalol concentrations but it is unclear if this is clinically significant. 53,116…”