Preliminary pharmacokinetics of the new antitussive compound vadocaine hydrochloride in animals.
The absorption and fate of vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) was studied using both unlabelled compound (rabbits, rats and dogs) and tritium-labelled compound (rats). Although vadocaine was orally absorbed in dogs, no oral absorption was found in the rabbits. The elimination of the intravenously given compound was very fast (t1/2 only about 0.6 h in the rabbits). Most of the drug was metabolized both in rats and dogs. In rats, less than 0.2% of the compound was found intact in 24-h urine. In dogs, the 24-h recovery was 1-5% of the dose. After intravenous injection to rats, 43% of the radioactivity given as tritium-labelled vadocaine was recovered in urine and 19% in faeces. After oral dosing, 37% was recovered in urine and 31% in faeces. Hence, the total 7-day recovery of the radioactivity given as tritium-labelled vadocaine was 62-68% of the dose.
Mäntylä
R
R
Research Centre, Orion Pharmaceutica, Espoo, Finland.
Männistö
P T
PT
Vuorela
A
A
Nissinen
E
E
D000284:Administration, Oral; D000818:Animals; D000996:Antitussive Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D004285:Dogs; D005260:Female; D006207:Half-Life; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats
D000996:Antitussive Agents; D010880:Piperidines; C051410:vadocaine