Referenced in: none

Automatically associated channels: Kv11.1

Title: Famotidine does not induce long QT syndrome: experimental evidence from in vitro and in vivo test systems.

Authors: Atsushi Sugiyama, Yoshioki Satoh, Akira Takahara, Yuji Nakamura, Masao Shimizu-Sasamata, Shuichi Sato, Keiji Miyata, Keitaro Hashimoto

Journal, date & volume: Eur. J. Pharmacol., 2003 Apr 11 , 466, 137-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12679150

Abstract
The effects of famotidine on the cardiac repolarization process were assessed using four different levels of test systems described in the draft stage guideline ICH S7B. A supratherapeutic concentration of famotidine (10(-5) M), which is >8 times higher than C(max) obtained after its therapeutic dose, neither inhibited human ether-a-go-go-related gene (HERG) K(+) current expressed in human embryonic kidney 293 (HEK293) cells nor affected any of the action potential parameters of guinea pig papillary muscles. Therapeutic (0.3 mg/kg, i.v.) to supratherapeutic doses (3-10 mg/kg, i.v.) of famotidine did not affect the repolarization process of the halothane-anesthetized canine model, while only supratherapeutic doses exerted the positive chronotropic, inotropic and dromotropic effects without affecting the mean blood pressure. Moreover, supratherapeutic doses of famotidine (1-10 mg/kg, i.v.) neither induced torsades de pointes nor prolonged QT interval in the canine chronic atrioventricular conduction block model. These results suggest that famotidine possesses no cardiovascular effects at a therapeutic dose, while it may exert cardiostimulatory actions after drug overdoses that might potentiate the proarrhythmic potential of co-administered cardiotonic agents by increasing the intracellular Ca(2+) concentration.