Probucol-induced QT prolongation and torsades de pointes.

Abstract

Probucol administration of 4 weeks produced torsades de pointes associated with exacerbated QTinterval prolongation in a 36-year-old womanwith Romano-Wardsyndrome. With discontinuance of probucol, the QTinterval corrected for rate shortened from 620 msec to 500 msec and ventricular ectopic beats disappeared completely. Although probucol is known to prolong the QTinterval, associated ventricular tachyarrhythmia has not been reported in humansas yet. This case suggests that one should be very careful in the administration of probucol to patients with long baseline QT intervals.

An Early‐Stage Atherosclerosis Research Model Based on Microfluidics

“…In addition, probucol prolongs the QT interval of the electrocardiogram. Such a change in QT interval is associated with malignant arrhythmias . Strikingly, in this study, we not only found anti‐oxidant activities of probucol, but also its destruction of endothelial cell–cell connections on the early‐stage AS model (Figure C).…”

“…Such a change in QT interval is associated with malignant arrhythmias. [ 60,61 ] Strikingly, in this study, we not only found anti-oxidant activities of probucol, but also its destruction of endothelial cell-cell connections on the early-stage AS model (Figure 5 C). The destruction effect of probucol on ECs monolayer integrity may promote the infi ltration of oxidized LDL and infl ammatory cells which are the initial stage of AS progression.…”

Identification of IKr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

“…Probucol is a cholesterol-lowering drug that has been found to cause long QT syndrome and torsades de pointes arrhythmia in patients and sudden cardiac death in experimental animals (Elharrar et al, 1979;McCaughan, 1982;Browne et al, 1984;Dujovne et al, 1984;Matsuhashi et al, 1989;Tamura et al, 1994;Reinoehl et al, 1996;Hayashi et al, 2004). Our data indicate that chronic probucol exposure reduces the hERG current with an IC 50 of 10.6 M and reduces native I Kr with an IC 50 of 20.6 M. We chose 48-h treatment of cells with probucol because the turnover of the hERG channel occurs at a rather slow rate (approximately 11 h) (Ficker et al, 2003).…”

Clinical Relevance and Management of Drug‐Related QT Interval Prolongation

“…274 Yet, case reports of QT prolongation and development of torsade de pointes or syncope were published. 275,276 Results of additional investigations suggest that QTc prolongation is likely to appear in female patients and in patients with long baseline QTc or with low serum albumin levels. 277,278…”