[Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs].
Olopatadine hydrochloride (olopatadine), a novel antiallergic agent, is effective in the treatment of allergic rhinitis, chronic urticaria, eczema and dermatitis. It has been reported that terfenadine and astemizole cause side effects on the circulatory system such as QT prolongation followed by serious ventricular arrhythmias (torsades de pointes). To investigate the possibility of QT prolongation, we used both conscious normal dogs and hypokalemia-anesthetized dogs under two conditions: 1) olopatadine used alone and 2) olopatadine used in combination with itraconazole, the CYP3A4-inhibiting antifungal agent, in the present investigation. The group treated with terfenadine alone (30 mg/kg, p.o.) and the group treated with a combination of terfenadine (10 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) had a significantly prolonged QT interval. On the other hand, the group treated with olopatadine alone (30 mg/kg, p.o.) and the group treated with a combination of olopatadine (30 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) did not show any significant changes in QT interval. Moreover, olopatadine (1 and 5 mg/kg, i.v.) did not influence the QT interval in hypokalemia-anesthetized dogs. These results suggest that there is very little possibility of QT prolongation as a result of clinically used olopatadine.
Iwamoto
K
K
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.
Ikeda
J
J
Nito
M
M
Kosaka
N
N
Ichikawa
S
S
Kobayashi
H
H
Ohmori
K
K
D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003990:Dibenzoxepins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006996:Hypocalcemia / Q000503:physiopathology; D017964:Itraconazole / Q000008:administration & dosage / Q000494:pharmacology; D000069605:Olopatadine Hydrochloride; D013686:Telemetry
D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride; D017964:Itraconazole