Parametrization by non-linear regression and bayesian estimation of bentazepam in a multiple dosage regimen in humans

The plasma levels of bentazepam were determined by an HPLC technique in a total of 10 patients receiving the drug orally in pill form who were on a dosage regimen with the drug administered every 8, 12 or 24 h. Blood samples were taken three times following the administration of the first and last dose and at times, immediately after the administration of intermediate doses. The parameters corresponding to a one-compartment kinetic model were calculated in each patient by using all the data on plasma levels still corresponding to different administrations by non-linear regression and applying programs with homoscedastic, heteroscedastic and bayesian estimation. The absorption constant had mean values of 2.33, 2.18 and 2.75 h-1. The elimination constant proved to be equal to 0.10, 0.09 and 0.22 h-1 while for the apparent distribution volume mean values of 1.89, 2.89 and 0.80 l/kg were found with each of the estimation programs employed, respectively. The values found for each of the kinetic parameters and with each of the programs were subjected to the non-parametric Kruskal-Wallis test with a view to detecting the presence or absence of statistically significant differences. The discrimination of the program that yielded the best fit was performed by linear regression between the values found for the plasma calculations and those calculated theoretically at the same time with each of the programs.