PHARMACOKINETIC STUDY OF BIOEQUIVALENCE OF ORODISPERSIBLE PHENAZEPAM TABLETS

Abstract

In order to confirm the bioequivalence of the new, orodispersible (ODT) dosage form of the phenazepam® and its traditional oral form, an open randomized study of comparative pharmacokinetics, bioequivalence and safety of these forms in 1mg single dose was conducted in 48 healthy volunteers. The duration of the study period of the drug›s pharmacokinetics was 72 hours. The total duration of the study for each volunteer was a maximum of 39 days (collection of information about adverse events, comparative analysis of the safety profiles). The average maximum concentration ( C _max) of the active substance in the blood plasma samples of volunteers when taking the studied ODT drug was reached after 1.95 h ( T _max) (in the range of 0.67 to 4.00 h), and when taking an oral comparison drug-after an average of 2.73 h (in the range of 1.00 to 12.00 h) and was 10.61 ng/ml and 10.34 ng/ml, respectively. The average square area under the pharmacokinetic curve “concentration - time” from the moment of taking the drug to the last blood sample with the determined concentration of the active substance at the point of 72 hours ( AUC _0-72) was 376.59 h × ng/ml when taking the test ODT drug and 378.44 h × ng / ml when taking the oral comparison drug. Analysis of the pharmacokinetic curves showed that the confidence intervals calculated for the difference in the mean values of C _max and AUC_{0- t} in the logarithmic scale with subsequent reverse conversion ( C _max = 1.03 (0.92÷1.15) and AUC _{0- t} = 0.99 (0.88÷1.13), that correspond to the conditions for accepting bioequivalence (0,8÷1,25). There were no significant differences in tolerability profiles.