Open-loop feedback control of serum bentazepam concentrations and Bayesian estimation in multiple dosage regimens in patients.
The time course of serum levels of bentazepam was studied in 10 patients receiving anxiolytic agent orally at a dose of 25 mg on multiple dosage regimens with dosage intervals of 8 and 12 h. Using the methods of "open-loop feedback control", no linear regression programs and Bayesian estimation, it was possible to establish the best estimates of the pharmacokinetic parameters corresponding to the single-compartment model for each patient from all their data relating to the serum levels obtained after the first dose and after multiple dosing with different regimens. The application of the Kruskal Wallis test showed that there were only statistical differences for the absorption constant, determined with and without Bayesian estimation. However, no statistically significant differences were found on comparing the experimentally obtained serum levels with the corresponding theoretical values calculated independently for each patient from the parameters established with and without Bayesian estimation. As population pharmacokinetic parameters of bentazepam, the following were established: Ka = 2.330 +/- 0.665 l/h; Vd = 1.209 +/- 0.546 l/Kg and Ke = 0.160 +/- 0.118 l/h, corresponding to a mean value for the elimination half-life of 4.33 h.
Colino
C I
CI
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Salamanca, Spain.
Lastra
C F
CF
López
F G
FG
Ledesma
A
A
Mariño
E L
EL
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001381:Azepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013030:Spain; D014149:Tranquilizing Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D001381:Azepines; D014149:Tranquilizing Agents; C006129:bentazepam