Research Article | Volume: 4, Issue: 12, December, 2014

Estimation of Pharmacokinetic Parameters Using Nonlinear Fixed Effects One Compartment Open Model

Mithun Kumar Acharjee Uttom Kumar Sitesh Chandra Bachar Wasimul Bari   

Open Access   

Published:  Dec 29, 2014

DOI: 10.7324/JAPS.2014.41210

Pharmacokinetics (PK) is the science of the kinetics of drug absorption, distribution and elimination. Statistical methods are usually used for PK parameter estimation producing nonlinear responses where drug effect mechanism is modeled using compartmental approach. In the present study, PK parameters were estimated with nonlinear fixed effects one compartment open model where drug dose and sampling time are covariates and the plasma drug concentration is dependent variable. The PK parameters namely absorption rate constant (a), elimination rate constant (b) and apparent volume of distribution (V) were estimated using nonlinear least square method for each individual separately and for all individuals collectively with longitudinal or multiple response plasma drug concentration-time data obtained from 24 healthy human volunteers with reference drug product of Atorvastatin. The estimates for combined data were â =0.13±0.13hr-1, (b ) Ì‚=0.49±0.13hr-1, (V ) Ì‚=248±0.05L. All the individuals were again stratified into three categories based on Body Mass Index (BMI) and the PK parameters were estimated for each stratum accordingly (stratum-normal: â=0.12±0.17hr-1, b Ì‚=0.47±0.17hr-1, V Ì‚=250.24±0.07L; stratum-overweight: â =0.15±0.24hr-1, (b ) Ì‚=0.47±0.25hr-1, (V ) Ì‚=267.25±0.09L; stratum-underweight: â =0.13±0.13hr-1, b Ì‚=0.49±0.13hr-1, V Ì‚=245±0.05L).

Keyword:     Compartmental Model Nonlinear Fixed Effects Model Nonlinear Least Square Method Pharmacokinetics Pharmacokinetic Parameters Estimation.


Mithun Kumar Acharjee, Uttom Kumar, Sitesh Chandra Bachar , Wasimul Bari. Estimation of Pharmacokinetic Parameters Using Nonlinear Fixed Effects One Compartment Open Model. J App Pharm Sci, 2014; 4 (12): 056-059.

Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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