Effect of oxatomide, an antiallergic agent, on QT interval in dogs.
Oxatomide (CAS 60607-34-3, KW-4354) is an effective antiallergic agent for allergic rhinitis, urticaria, pruritus cutaneous, and eczema/dermatitis, etc. Terfenadine (CAS 50679-08-8) and astemizole (CAS 68844-77-9), antiallergic agents, have been reported to induce QT prolongation leading to serious ventricular arrhythmia (torsades de pointes) as cardiovascular adverse effects. The present study was carried out to determine whether oxatomide and terfenadine have effects on QT interval as a single drug or in combination with itraconazole (CAS 84625-61-6), an antifungal agent with a CYP3A4 inhibitory effect, in conscious dogs. Terfenadine alone induced QT prolongation at the dose of 30 mg/kg p.o. When itraconazole was administered at the dose of 100 mg/kg p.o. 1 h before terfenadine administration, terfenadine induced QT prolongation at the dose of 10 mg/kg p.o. On the other hand, oxatomide did not induce QT prolongation either as a single agent at the dose of 30 mg/kg p.o. or in combination with itraconazole at the dose of 10 mg/kg p.o. The results present no evidence that oxatomide has the potential to provoke ventricular arrhythmia.
Iwamoto
K
K
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Ikeda
J
J
Nito
M
M
Kosaka
N
N
Ichikawa
S
S
Ohmori
K
K
Sakai
K
K
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004285:Dogs; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D017964:Itraconazole / Q000494:pharmacology; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology*; D013686:Telemetry
D018926:Anti-Allergic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010879:Piperazines; D017964:Itraconazole; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C015408:oxatomide