EFFECTS OF DESETHYLAMIODARONE ON THE ELECTROCARDIOGRAM IN CONSCIOUS FREELY MOVING ANIMALS: PHARMACOKINETIC AND PHARMACODYNAMIC MODELING USING COMPUTER-ASSISTED RADIO TELEMETRY
✍ Scribed by Jahanavi Kharidia; Natalie D. Eddington
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 666 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
Desethylamiodarone (DEA), the mjor active metabolite of amiodarone (AMD), plays a significant role in the electrophysiological effects observed during AMD thexapy. The pharmacokinetics and pharmacodynamics of DEA wcre studied in rats. Animals were administered DEA (20 or 40 mg kg-I) 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 w i t h a tlm of 54-8 and 46.2 h after the 20 and 40 mg kg-I doses, respectively. The relationship between DEA and the QT interval or T amplitude was best described by a sigmoid Emodel. The mean ( f SD) E,, for QT and T ampKtude was 32-23 (f 2.49% and 0-12( f 00.9) mV, respectively. The mean ( f SD) EC, value was 297.5 ( f 22-80) ng ml-for QT and 139.8 ( f 28.69) ngmL-' for the T amplitude. The elcctmphysiological 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.