Sotalol drug therapy is frequently employed to prevent the recurrence of highly symptomatic atrial fibrillation or flutter (AF, AFb). Sotalol can cause QTc prolongation that is proportional to blood concentration. Excessive concentration can cause Torsade de Pointes ventricular tachycardia (TdP). Because the risk of TdP, initiation of oral sotalol therapy is mandated by FDA to be in-hospital for a minimum of three days under ECG monitoring with facilities and personnel able to provide cardiac resuscitation. With oral administration (bid), 3 days are needed to reach maximal steady-state blood concentrations (Cmax ss) and thus maximal QTc prolongation. Three hospital days in a telemetry bed is costly and considerable expenditure of time and resources. Availability of IV sotalol makes it possible to reduce the loading time from 3 days to 1 day. The IV to oral loading regimen has been developed by model informed drug development. Serum sotalol concentrations and corresponding QTc were obtained from a previously performed bioequivalence study in healthy volunteers who received a single dose of oral and IV sotalol. NONMEM software package was used for population pharmacokinetic modeling and simulation. First Order Conditional Estimation method with Interaction (FOCE-INTER) was used for computation. We chose to administer IV sotalol over 1 hour to obtain Cmax ss target in a timeframe convenient for medical staff to supervise. The simulation for loading to the Cmax target produced by 80 mg PO bid is shown in the Figure; 60 mg IV sotalol is administered over 1 hour followed by 80 mg oral sotalol at 5 hours from start of infusion end then a second oral dose of 80 mg at 12 hours. One can target 120 mg maintenance dose by loading 90 mg IV over 1 hr followed by 120 mg oral dosing. Sotalol concentration will peak in 2-4 hours following each oral administration, thus in 21 hour there will be 3 sotalol peak concentrations. This permits evaluation of QTc response and risk of TdP all within a 1 day admission.
Absence of QTc Prolongation with Sodium N-(8-[2-Hydroxybenzoyl] Amino) Caprylate (SNAC), an Absorption Enhancer Co-Formulated with the GLP-1 Analogue Semaglutide for Oral Administration
