RELATIVE BIOAVAILABILITY OF DIFFERENT BUTAMIRATE CITRATE PREPARATIONSAFTER SINGLE-DOSE ORAL-ADMINISTRATION TO 18 HEALTHY-VOLUNTEERS

Eighteen volunteers have been treated with different oral formulations of butamirate citrate according to 2 randomized 2-way crossover desig ns. In the first study (study I) the test preparation was a syrup (Dem otussol Hustensirup, Demopharm), and the reference preparation was a s yrup already marketed (Sinecod Sirup, Zyma SA), A test preparation (De motussol Tabletten) was compared to a solution (Demotussol Hustentropf en) in the second study (study II). Within the 2 study periods the vol unteers received single 45 mg doses of the test and the reference form ulation, respectively. Blood samples have been drawn immediately prior to each administration and at 17 sampling points within 96 h after do sing. A wash-out period of 1 week was maintained between successive dr ug doses. The plasma concentration of one of the main metabolites, 2-p henylbutyric acid, was determined by a validated reversed-phase HPLC m ethod with UV detection, with a lower limit of quantification of 50 ng /ml. The following mean values have been obtained in study I (syrup pr eparations) for the test: AUC(0-infinity) 46.9 mu g X h/ml, C-max of 1 .77 mu g/ml at 1.1 h, t(1/2) 28 h and after administration of the refe rence: AUC(0-infinity) 50.4 mu g x h/ml, C-max 1.86 mu g/ml, t(max) 1. 5 h, t(1/2) 26 h. In study II the following mean values have been obta ined for the test preparation (tablet): AUC(0-infinity) 54.7 mu g x h/ ml, C-max of 1.88 mu g/ml at 1.1 h, t(1/2) 27 h and for the reference (solution): AUC(0-infinity) 54.5 mu g X h/ml, C-max 1.94 mu g/ml, t(ma x) 1.1 h, t(l/2) 26 h. Both preparations have been proven to be bioequ ivalent to their corresponding references regarding extent and rate of absorption.