JGuiB AN ASSISTANT TOOL FOR PHARMACOKINETICPHARMACODYNAMIC

1
JGuiB - AN ASSISTANT TOOL FOR PHARMACOKINETIC/PHAR
MACODYNAMIC MODELING WORKING WITH BOOMER
Ying-hao Lu1, David W.A. Bourne2, Yung-jin
Lee1 1College of Pharmacy, Kaohsiung Medical
University, Kaohsiung, Taiwan 2College of
Pharmacy, University of Oklahoma Health Sciences
Center (OUHSC), Oklahoma City, OK 73119, U.S.A.
Table 1 - Comparison of BOOMER and JGuiB (
BOOMER)3
Keywords BOOMER, JGuiB, PK/PD Modeling,
Non-linear Regression, Java, Java SE
Introduction BOOMER (www.BOOMER.org) created by
David W.A. Bourne is an excellent non-linear
regression tool for data analysis and modeling of
pharmacokinetic (PK) and pharmacodynamic (PD)
data.1 It is very suitable for purposes of
computer-aided PK/PD modeling teaching and data
analysis with many built-in numerical integration
and nonlinear optimization algorithms.
Unfortunately, BOOMER only runs in a menu driven
mode under different platforms. Therefore it may
take time for a beginner to learn how to use it
in PK/PD modeling. The purpose of this study was
to build a GUI (Graphical User Interface) for
BOOMER to assist users who need a GUI to
manipulate the operation of BOOMER.
from each batch file from each project
file (JGuiB can generate many batch files)
a. support some project files for examples. b.
visualized model graphs in built-in library.
c. helpful video demo when linking to JGuiB
website (http//jguib.pkpd.org.tw/). d. parameter
type lists, parameter properties lists, error
type lists. BOOMER Version (Mac OS X, Windows,
Linux 3.3.2), JGuiB Version (2.1)
Table 2 - Comparison of JGuiB ( BOOMER) and
WinNonlin4
Methods and Materials When starting to build the
GUI, the first problem we had to solve was to
modify BOOMER to accept command-line
instructions. In order to make the GUI work with
BOOMER under background, BOOMER was modified to
be able to run under command-line mode. This
allowed the operation of BOOMER controlled by the
GUI generated batch files. Since BOOMER has the
cross-platform property to run on Mac OS X,
Windows and Linux, our GUI should exploit this
property. Thus we selected Java (Java SE) as
programming language to build our GUI, and used
JBuilder X Foundation, a powerful Java IDE
(Integrated Development Environment), as
developer and compiler. We call this GUI as
JGuiB, which stands for Java GUI for BOOMER.
BOOMER allows explicit entry of weight as
third data column, but JGuiB just supports the
weighting scheme selections for the data sets. a,
b, c, d - constants Physiologically-Based
Pharmacokinetic Non-Compartmental Analysis
Results and Discussion We have successfully
turned the menu-driven mode of BOOMER into a
GUI-based application with JGuiB. JGuiB with
BOOMER can run in platforms of Mac OS X, Windows
and Linux. Three main BOOMER functions in PK/PD
modeling are supported normal fitting,
simulation and Bayesian estimation. Users just
follow the sequences of PK/PD modeling (model
building/selection), data manipulation
(spreadsheet-like data editing copy and paste)
and weighting scheme selections, and finally
numerical integration/nonlinear optimization
selections through GUI and run this project with
BOOMER. Twenty four frequently used PK/PD models
with graphics were built and included with JGuiB.
JGuiB also allows users to build their defined
PK/PD models with a panel ofParameter Table,
such as physiologically based pharmacokinetic
(PBPK) model. To avoid possible input errors
made by users, JGuiB is designed to lessen users
inputs, such as without assigning lower limit
and upper limit for each adjustable parameter.
Two of more fascinating functions of JGuiB are
that (1) it provides the clinical-oriented
Bayesian estimation functions with
multiple-dosing modeling functions for uniform or
non-uniform doses,2 and (2) it enables BOOMER to
simultaneously work with different PK/PD models
(max. 4 models in one project file) using the
same set of data for the purpose of model
discrimination (Figure 1). We contrast BOOMER
with JGuiB plus BOOMER in Table 1,3 and compare
JGuiB plus BOOMER with WinNonlin in Table 2.4
Finally there are the screenshots of JGuiB to
show how to use it with friendly-to-use functions
in Figure 2.
Figure 1 - JGuiB ( BOOMER) can generates 20
output files in the same subject data working
with 4 PK/PD models.
Conclusion and Future Works JGuiB has been
successfully built and it is just a GUI, an
assistant tool for BOOMER in PK/PD modeling. It
generates a batch file (Input file) which is
subsequently analyzed using BOOMER which provides
the computational engine. Therefore, JGuiB is
dependent on BOOMER. The built-in PK model
library in JGuiB enables users to apply these
models quickly to analyze data with BOOMER.
Boomer also can easily apply to multiple dosing
modeling and Bayesian estimation into the field
of clinical pharmacokinetic services with
excellent model building templates and
easy-to-use data management of JGuiB. Therefore,
JGuiB effectively extends the abilities of
Boomer. In conclusion, JGuiB is the first GUI
program for individual PK/PD software in the
world. In the future, we plan to enhance the
modeling automation of JGuiB to include PBPK
modeling and Monte Carlo simulation. In
addition, we will continue to develop JGuiB
including more functions provided by BOOMER, and
enhance its ease of use. JGuiB can be freely
downloaded from http//jguib.pkpd.org.tw/.
Figure 2 - the screenshots of JGuiB to show how
to use it with friendly-to-use functions.
References 1.Bourne DWA, BOOMER, 1989, a
simulation and modeling program for
pharmacokinetic and pharmacodynamic data
analysis. Computer Methods and Programs in
Biomedicine, 29 191-95 2.Yamaoka K, Nakagawa T,
Tanaka H, Yasuhara M, Okumura K, Hori R, 1985, A
nonlinear multiple regression program, MULTI2
(BAYES), based on Bayesian algorithm for
microcomputers. Journal of Pharmacobio-Dynamic,
8 246-56.
3.Boomer Website, 2006, http//www.BOOMER.org
4.WinNonlin Website, 2006, http//www.pharsight
.com/products/winnonlin/