Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion

Area of Science:

• Pharmacology
• Cardiology
• Drug Development

Background:

• Sotalol is used for atrial flutter/fibrillation but requires a 3-day in-hospital loading period due to QT prolongation risks.
• Current oral sotalol administration necessitates a 3-day period to reach maximum concentration and QT prolongation in patients with normal renal function.

Purpose of the Study:

• To develop an intravenous (IV) to oral sotalol loading regimen.
• To shorten the in-hospital initiation or dose escalation period from 3 days to 1 day.
• To ensure patient safety is maintained during the reduced initiation period.

Main Methods:

• Model-informed drug development techniques were utilized.
• Simulations were performed for sotalol therapy initiation and dose escalation.
• An IV loading dose followed by oral sotalol administrations was modeled.

Main Results:

• A 1-day regimen was developed for patients with normal renal function.
• This regimen includes an initial 1-hour IV loading dose followed by two oral doses within 24 hours.
• The regimen achieves maximum serum concentrations reflecting maximum QT prolongation within the 1-day observation period.
• Dosing regimens were also developed for patients with impaired renal function.

Conclusions:

• An IV to oral sotalol loading regimen enables safe initiation or dose escalation in 1 day for patients with normal renal function.
• This approach significantly reduces the 3-day oral dosing regimen requirement.
• The developed regimen maintains patient safety while optimizing sotalol therapy initiation.