Population kinetics and conditional assessment of the optimal dosage regimen using the P-PHARM software package.
The adjustment of individual dosage regimen is an adaptive control process based upon an individual response to a pharmacokinetic model. To attain this objective, it is very helpful to know the characteristics of the population to which the subject belongs, in terms of mean parameters and interindividual variability. Usually the available information consists of incomplete and sparse data. For this reason it is essential to employ a computational methodology based on non-linear mixed-effect procedures in order to obtain a population parameter estimate. A Bayesian methodology can then be applied from the population parameters to the specific data for the individual requiring a dosage adjustment (such data includes drug concentration(s) of the active drug, demographic data, etc). The result of the Bayesian calculation supplies the required individual pharmacokinetic parameters. An optimal dosage regimen can be defined on the basis of therapeutical criteria (concentration ranges) as well as practical constraints such as: the size of available unitary drug dosages, feasible drug intake times, penalties associated with expected concentrations falling outside the therapeutic concentration ranges. In this paper we present the methodology and results obtained using the P-Pharm software tool. P-Pharm implements a non-linear mixed-effect population parameter estimation algorithm based on the EM algorithm. This method allows the inclusion of explicit variables into the calculations, it implements an individual Bayesian parameter estimation procedure and also an algorithm for the conditional assessment of the optimal dosage regimen given a list of practical constraints.
Gomeni
R
R
SIMED, Créteil, France.
Pineau
G
G
Mentré
F
F
D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001499:Bayes Theorem; D003710:Demography; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008432:Mathematical Computing; D010599:Pharmacokinetics; D011153:Population; D012984:Software
D000970:Antineoplastic Agents