Pharmacokinetics of graded single doses of the novel antitussive compound vadocaine hydrochloride in healthy male volunteers.

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 properties. The pharmacokinetics of this new compound were studied in two Phase I clinical trials during safety evaluation. 6 (Part I) and 8 (Part II) healthy male volunteers participated in these studies. The pharmacokinetics were studied after single oral doses of 5, 10, 15, 20, 30 and 50 mg (Part I) and 100, 200, 300, 400 and 500 mg (Part II) of vadocaine in aqueous solution. Vadocaine was rapidly absorbed at each dose level. The AUCo----infinity value and 24-h urinary recovery of intact compound increased linearly as functions of the dose. The elimination half-life varied from 2.2 +/- 0.2 h to 3.7 +/- 1.6 h in a dose range from 5 to 50 mg, and from 2.7 +/- 0.3 h to 4.0 +/- 1.0 h in a dose range from 100 to 500 mg. The peak concentration of vadocaine after the highest dose was 2317.3 +/- 31.5 ng/ml at 1 h. When higher doses were used renal clearance did not change, although total body clearance seemed to diminish. Over 90% of vadocaine is metabolized, and the metabolic pathways may become saturated at a dose of 400 mg.