1237 Electrocardiographic effects of the 5-HT 3-R-antagonists

Abstract

5-HT3-R-antagonists are widely used to control the cytotoxic-caused emesis. Since Ondansetron has a detectable binding at non 5-HT3 sites (5–HT1b–1c) and Tropisetron at 5-HT4 and 5-HT2c -uptake sites and 5-HT receptors are found in the human cardiac atria, an arrhythmogenic potential of these drugs as a dose-dependent prolongation of the QTc interval cannot be excluded. Aim of our study was to evaluate the QT interval on the surface ECG expressed as the rate corrected maximum interval according to Bazett (QTc = QT/√R–R) before (T0) and after at least 3 cycles of therapy (T1–T2–T3). In 121 cancer pts (97 females; PS 0–1; from 31 to 72 years), treated with > 60 mg/m2 cisplatinincluding (45 pts) or not chemotherapies plus Ondansetron (16 mg i.v. day 1 + 16 mg p.o. on day 2–5; 46 pts) of Granisetron (3 mg Lv. day 1; 41 pts) or Tropisetron(5 mg i.v. day 1 + 5 mg p.o. on day 2–5; 34 pts). Results are T0 T1 T2 T3 ONDA 0.394 0.389 0.397 0.380 (P 0.980) (P 0.816) (P 0.597) (P 0.643) GRANI 0.398 0.407 0.407 0.402 (P 0.836) (P 0.622) (P 0.650) (P 0.464) TROPI 0.391 0.385 0.394 0.398 Values of QTc little higher than the max normal range (never pathologic) were found at To in 6 pts (2 ONOA, 2 GRANl, 2 TROPl) and in 12 pts during the cycles (6 ONOA, 3 GRANI, 3 TROPl). In conclusion the three 5-HT3 drugs at ordinary doses are not surely responsible for arrhythmic effects; on the other hand the slight increase of the QTc that we found may be correlated with the antiblastic agents itself (as doxorubicin) and/or concomitant medications (as hyperydration in cisplatin therapy).