Simulation of plasma bentazepam levels in multiple dosage regimens from parameters established by non-linear...

In the present study, a simulation was made of the time-course of the plasma levels of bentazepam, administered orally at a dose of 25 mg with dosage intervals of 8, 12 and 24 h over 5 days of treatment. The pharmacokinetic parameters corresponding to a single-compartment model were calculated in a previous study with 10 patients who received the drug in a multiple dosage regimen, using all the data relating to plasma levels even though they corresponded to different administrations, by non-linear regression employing programs based on homoscedastic, heteroscedastic and bayesian estimation methods. The mean values of the kinetic parameters obtained previously and used in the present study were as follows: for the absorption constant, mean values of 2.33, 2.18 and 2.75 h-1 were used; for the elimination constant, the values used were 0.10, 0.09 and 0.22 h-1 and for the apparent distribution volume, the values used were 1.89, 2.89 and 0.80 l/kg, with each of the above-mentioned calculation programs, respectively. The highest value for the maximum concentration at steady state proved to be 313.2 ng/ml for a dosage interval of 8 h according to the parameters established with the program using homoscedastic estimation. In the same case (homoscedastic estimation) the highest value of the minimum at steady state was 168.7 ng/ml. By contrast, the lowest value of the maximum value at steady state--129.3 ng/ml--was obtained with a dosage interval of 24 h using the parameters of the heteroscedastic estimation method, while the lowest value of the corresponding minimum was also observed for an interval of 24 h but using the parameters of the bayesian estimation; this was 2.8 ng/ml.