Assessment of the safety margin of vadocaine hydrochloride in man.
Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) is an anilide derivative with antitussive and local anaesthetic action. The safety of this new compound was studied in 8 healthy male volunteers in a Phase I clinical trial. Vadocaine was administered orally as a single dose of 50, 100, 200, 300, 400 and 500 mg. At the two highest dose levels used, 400 and 500 mg, vadocaine induced side-effects originating in the central nervous system; ECG analysis revealed small prolongations in the P-Q interval and QRS complex after 400 and 500 mg. At a dose of 500 mg the P-Q interval was prolonged by a maximum of 38% (184 ms at 0.5 h; 134 ms pre-dose). The compound had no effect on blood and urinary parameters measured for safety evaluation. On the basis of these results, a 300 mg dose of vadocaine appears to be safe in man in all respects. This dose level is 10 times the therapeutic dose (30 mg). Vadocaine is sufficiently safe for future clinical trials in patients with cough.
Karttunen
P
P
Orion Corporation Ltd., Orion Pharmaceutica, Medical Department, Kuopio, Finland.
Uusitupa
M
M
Helin
M
M
Tukiainen
H
H
Silvasti
M
M
D000328:Adult; D000996:Antitussive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects*
D000996:Antitussive Agents; D010880:Piperidines; C051410:vadocaine