Pharmacokinetic/Pharmacodynamic Analysis of Quinidine‐Induced Dominant Frequency Reduction in Thoroughbred Horses With Atrial Fibrillation

ABSTRACT

Quinidine has long been used for the pharmacological treatment of atrial fibrillation (AF) in horses; however, the plasma concentration required for conversion to sinus rhythm remains unclear. Dominant frequency (DF), derived from surface electrocardiograms, reflects atrial activation rate during AF. This study aimed to quantify the relationship between plasma quinidine concentration and DF using a pharmacokinetic/pharmacodynamic (PK/PD) approach. Ten Thoroughbred horses with naturally occurring AF received quinidine sulfate via a nasogastric tube. Plasma quinidine concentrations and DF values, calculated from digitized atrial fibrillatory segments, were measured during treatment. PK/PD was analyzed using a sigmoid inhibitory E _max model, with typical parameters including a baseline DF of 6.27 Hz, a maximal DF reduction of 3.63 Hz, a theoretical minimum DF of 2.64 Hz, an EC ₅₀ of 0.78 μg/mL, and a Hill coefficient of 1.81. Nine horses converted to sinus rhythm, with median DF decreasing from 6.4 Hz to 3.0 Hz immediately before conversion. Model simulations indicated a pharmacodynamic plateau, with an increase in plasma quinidine concentration from 4 to 5 μg/mL resulting in only a 0.06‐Hz reduction in DF. A model‐predicted plasma quinidine concentration of 2.6 μg/mL achieved a DF of 3.0 Hz and may represent a target concentration for conversion.