Steady state pharmacokinetics of the new antitussive compound vadocaine hydrochloride.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methyl-piperidyl) propionanilide hydrochloride, OR K-242-HCl) is a novel compound, which chemically resembles amide-type local anaesthetics. Vadocaine has been proved to be an antitussive drug both in animal and in human studies. The steady state pharmacokinetic profile of vadocaine and its main metabolite in healthy volunteers after a dosage of 30 mg t.i.d. for seven days were studied. The safety of vadocaine was evaluated by ECG monitoring and by hematological and biochemical laboratory tests. Blood and urine samples were taken on the 1st, 3rd and 7th days of the study. The peak concentrations of vadocaine were on the 1st day 72.9 +/- 6.5 ng/ml at 1 h, on the 3rd day 86.4 +/- 10.3 ng/ml at 1.5 h, and on the 7th day 86.4 +/- 7.0 ng/ml at 1.5 h. AUC0-infinity values were 327.0 +/- 43.1, 449.6 +/- 81.0 and 430.5 +/- 77.1 (ng/ml)h, respectively. No side-effects or any clinically significant changes in ECG or laboratory tests were detected during the study. According to the serum concentrations and pharmacokinetic parameters the steady state level was achieved already after the third 30 mg dose of vadocaine. No cumulation of intact compound or its metabolite was seen during the study.