Abstract | OBJECTIVES: BACKGROUND: QT interval prolongation and torsade de pointes are associated with astemizole intake and have been ascribed to block the repolarizing K+ currents, specifically the rapidly activating component of the delayed rectifier iKr. Astemizole undergoes extensive first-pass metabolism, and its dominant metabolite, desmethylastemizole, has a markedly prolonged elimination time. We report the clinical observation of QT prolongation and torsade de pointes in a patient with undetectable serum concentrations of astemizole (< 0.5 ng/ml) and "therapeutic" concentrations of desmethylastemizole (up to 7.7 ng/ml or 17.3 nmol/liter). METHODS: The perforated patch clamp recording technique was used to study the effects of desmethylastemizole (20 nmol/liter) on action potentials and iKr in isolated rabbit ventricular myocytes. RESULTS:
Desmethylastemizole produced action potential prolongation and the induction of plateau early afterdepolarizations. Under voltage clamp conditions, desmethylastemizole suppressed iKr amplitude by approximately 65%. The drug E-4031 (100 nmol/liter), which selectively blocks iKr, had a similar effect on current amplitude. CONCLUSIONS:
|
Authors | V R Vorperian, Z Zhou, S Mohammad, T J Hoon, C Studenik, C T January |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 28
Issue 6
Pg. 1556-61
(Nov 15 1996)
ISSN: 0735-1097 [Print] United States |
PMID | 8917271
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Histamine H1 Antagonists
- Potassium Channels
- Astemizole
- desmethylastemizole
|
Topics |
- Aged
- Aged, 80 and over
- Animals
- Astemizole
(adverse effects, analogs & derivatives, blood)
- Electrocardiography
(drug effects)
- Female
- Heart
(drug effects)
- Heart Arrest
(blood, chemically induced, physiopathology)
- Histamine H1 Antagonists
(blood)
- Humans
- Potassium Channels
(drug effects)
- Rabbits
- Torsades de Pointes
(blood, chemically induced, physiopathology)
|