Desethylamiodarone (DEA), the major active metabolite of amiodarone (AMD), plays a significant role in the electrophysiological effects observed during AMD therapy. The pharmacokinetics and pharmacodynamics of DEA were studied in rats. Animals were administered DEA (20 or 40 mg kg-1) and blood samples were collected. The heart rate, PQ, QR, QS, QT, RR intervals, and P,R,S, and T amplitudes were also measured after dosing using telemetry. DEA followed a biexponential decline with a t1/2beta of 54 center dot 8 and 46 center dot 2 h after the 20 and 40 mg kg-1 doses, respectively. The relationship between DEA and the QT interval or T amplitude was best described by a sigmoid Emax model. The mean (+/- SD) Emax for QT and T amplitude was 32 center dot 23 (+/- 2 center dot 47)% and 0 center dot 12(+/- 00 center dot 9) mV, respectively. The mean (+/- SD) EC50 value was 297 center dot 5 (+/- 22 center dot 80) ng ml-1 for QT and 139 center dot 8 (+/- 28 center dot 69) ng mL-1 for the T amplitude. The electrophysiological changes observed with DEA are similar to those with AMD. These results further support the contribution of DEA to the efficacy noted during AMD therapy and provide and viable animal for continued description of this relationship.