One Day Hospital Initiation of Oral Sotalol The Cmax ss Test Strategy

BACKGROUND: Sotalol loading intravenously enables achieving blood levels of sotalol that are observed at maximal steady-state concentration (Cmax ss) in one-day permitting the measurement of maximum QTc effects. Rapid evaluation of the QTc effects permits determination of arrhythmic risk and thus permits discharge in 24-hours instead of the usual three-day oral load hospitalization. Given the expense of IV Sotalol an oral loading test strategy is presented that also achieves Cmax ss blood levels rapidly, permitting a one-day hospitalization for QTc evaluation. METHOD: Pharmacokinetic parameters referred to in the literature derived from normals as well as patients was utilized for population pharmacokinetic modeling and simulation.to obtain the Cmax ss concentrations for patients with normal renal function, creatinine clearance (CrCl) > 90 ml/min), as well as for patients with a CrCl of 60-89, 30-59, and 10-29 ml/min). Using pharmacokinetic simulations, an oral loading dose, as well as a second oral dose were determined that would reach the estimated Cmax ss in each of the groups based on renal function. RESULTS: For target dosing of 120 mg oral sotalol BID in patients with a CrCl >90 ml/min an oral loading dose of 200 mg provides a peak sotalol level of 1,420 ng/ml in 3-4 hours post dosing. The Cmax ss target is 1,299 ng/ml resulting in a 9% overshoot. The Cmax ss concentration provides a means of evaluating QTc effects within 24-hours. Oral loading regimens are described for varying additional renal function levels (CrCl 60-90, 30-59 and 10-29 ml/min) along with the time to first oral dose and follow-up dosing. The initial test dose can be based on an 80 or 120 mg oral sotalol maintenance dosing strategy. CONCLUSIONS: Employing an oral loading strategy may permit QTc evaluation and one-day discharge, preserving the pharmacoeconomic advantage of a Cmax ss test strategy.