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POPULATION PHARMACOKINETIC / PHARMACODYNAMIC MODELING :
EVALUATION OF MAXIMUM LIKELIHOOD EXPECTATION
MAXIMIZATION METHOD IN ADAPT 5
by
Min-Hyung Park
A Thesis Presented to the
FACULTY OF THE VITERBI SCHOOL OF ENGINEERING
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOMEDICAL EMGINEERING)
December 2006
Copyright 2006 Min-Hyung Park
Object Description
| Title | Population pharmacokinetic/pharmacodynamic modeling: evaluation of maximum likelihood expectation maximization method in ADAPT 5 |
| Author | Park, Min-Hyung |
| Author email | minhpark@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biomedical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2006-10-27 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-11-15 |
| Advisor (committee chair) | D'Argenio, David Z. |
| Advisor (committee member) |
Maarek, Jean-Michel Schumitzky, Alan |
| Abstract | Maximum likelihood estimation via the expectation maximization algorithm (EML) was implemented into ADAPT 5 to support population pharmacokinetic / pharmacodynamic studies. Two detailed simulation studies were conducted using a one compartment pharmacokinetic model with sparse data and a complex pharmacokinetic / pharmacodynamic model to evaluate this algorithm. Additionally, a population analysis of the minimal model for the intravenous glucose tolerance test in mice was performed as an example of biological study using real data. In the simple pharmacokinetic model, less than 1% mean prediction errors were obtained for the estimated population mean and covariance parameters. For the complex model, the EML estimation resulted in prediction error less than 8% for the mean parameters and these results were not influenced by different initial guesses for model parameters. The EML estimation for the animal study resulted in a correlation coefficient between predicted and measured values of glucose concentration in plasma of 0.97. |
| Keyword | population PK/PD; maximum likelihood; expectation maximization; IVGTT; minimal model; ADAPT |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m143 |
| Contributing entity | University of Southern California |
| Rights | Park, Min-Hyung |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-Park-20061115 |
| Archival file | uscthesesreloadpub_Volume40/etd-Park-20061115.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | POPULATION PHARMACOKINETIC / PHARMACODYNAMIC MODELING : EVALUATION OF MAXIMUM LIKELIHOOD EXPECTATION MAXIMIZATION METHOD IN ADAPT 5 by Min-Hyung Park A Thesis Presented to the FACULTY OF THE VITERBI SCHOOL OF ENGINEERING UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOMEDICAL EMGINEERING) December 2006 Copyright 2006 Min-Hyung Park |
