On-line Pharmacokinetic Simulation

by Guenther Hachous, University of Florida
Web Site

Review #1

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Hardware platform:

System software requirements:

Disciplines:

Price:

Description and comments:

The simulations allow the user to change one or more of the pharmacokinetic model parameters and then simulate the plasma concentration-time profile. Two different profiles can be simulated on the same plot in most of the simulations. This is very useful approach to demonistrate how each of the pharmacokinetic parameters affects the drug profile in the body. Because of the small plot size visualizing the effect of small changes in the pharmacokinetic parameters on the drug profile may be difficult. However the plot size can be increase in the off-line simulations.

The value of the simulations can be enhanced by providing some feed back Guided simulations

Rating Scale (1-5 with 5 best):

Contents:	2.5
Educational value:	4
Ease of use:	4
Performance:	3
User Interface/Navigation:	4
Interactivity:	4
Price:	5

Review #2

Title

On-Line Pharmacokinetic Simulations

Hardware and Software

This is a web site (http://www.cop.ufl.edu/safezone/pat/pha5127/simulatn.htm) which may be accessed using an internet browser and internet access. This reviewer used Netscape Communicator (V4.04) to review the site. There is no special requirement for hardware.

Description of the Site

General

The site consists of a collection of 9 separate simulation modules for an introductory pharmacokinetics course. The modules are IV Bolus Single Dose, IV Bolus Physiological Model, IV Bolus Metabolism, Oral Single Dose, Multiple IV Bolus, Multiple Oral Dosing, Single Dose Infusion, and Multiple Dose Infusion. In addition to these modules which may be run on line, the Excel version of the modules may be downloaded from the site and run on the client's computer, provided that the client has the Excel program. However, there are minor differences between the internet and Excel versions (please see below for details).

After clicking on each module, the user is provided with a screen which allows input of pharmacokinetic parameters and dosage regimen data for two scenarios. Additionally, the graphs of the plasma concentration-time data and other kinetic parameters are provided as output on the same screen. This allows the user to test the effects of a change in one or more kinetic/dosage data on the other kinetic parameters and the plasma-concentration-time courses. After changing the input parameters, the user is required to press "Plot" button which simulates the data and changes the output parameters and graphs.

Help Features

This reviewer was not able to locate any help tools for the simulations.

Price

The site is available to public free of charge.

Evaluation of the Program

Pharmacokinetic simulations are a component of most introductory pharmacokinetic courses. Although several simulation programs are available for this purpose, only few are on-line; a majority of the programs are stand alone modules requiring specific platforms. Therefore, a major advantage of this site is that students may use the site without any requirements for specific platforms or programs. Another advantage of the site is that the simulations are relatively fast and easy to carry out. Furthermore, the input parameters include clearance and volume of distribution (both independent parameters), as opposed to some simulation programs which require input for elimination rate constant or half life (dependent on V and Cl). Therefore, it is more consistent with the physiologic relationship among the major pharmacokinetic parameters. However, in the opinion of this reviewer, the modules could be improved in the following areas:

• Fixed Time (x) Axis: One of the major shortcomings of the on-line modules is that the time (x) axis in the simulated graphs is fixed at 24 hours. This is especially critical for multiple dosing (both IV and PO), where irrespective of number of doses (n), the simulation is carried out for 24 hr. This means that if the dosage interval is 12 or 24 hr, the graph is simulated for 2 or 1 (i.e. single dose) interval, respectively. Additionally, for IV Infusion, steady state may not be achieved in 24 hr.
• Y Axis: Except for the Single Dose IV Bolus module which allows both linear and semilog plotting, the other modules are graphed using a linear Y scale. Additionally, for the Single Dose IV module, the Y axis for semilog shows "0.00" for any value less than 0.1. This may be related to the programmed number of decimal points. The authors may consider using scientific numbers to avoid this problem. Further, for the IV Bolus Metabolism module, the y axis is fixed between 0.0001 and 1. Therefore, concentrations larger than 1 are plotted outside the axes.
• Units: For both PO and IV Multiple Dosing modules, the unit of concentration in the graph is mg/L. However, the units in the input data indicate a unit of µg/L (or ng/mL). Additionally, for the Physiologic module, the graph units are different than the units in the output data.
• Presentation Format: Using one screen for the input and output parameters may be problematic at times. In my experience with this type of simulations, students may enter the input parameters and without activating the simulation (or Plot) button, they may print the data, creating a mismatch between the input and output or graphs. An an alternative, the authors may create an input screen (without output) which leads to the output page. This creates an extra screen. However, I believe it is more appropriate.
• Glossary of Terms and Help: Although the simulations are relatively easy to carry out, there is no help available for them. Additionally, abbreviations are not defined (most terms are easily understandable, however). Addition of help and definition of models and terms using hypertexts would enhance the value of the site.
• Accuracy of the Modules: The modules tested appeared accurate in terms of outputs and graphs. However, when the Multiple IV Bolus module was tested with the following parameters (D: 8 mg; tau: 6 hr; CL: 40 L/hr; Vd: 20 L), the maximum plasma concentrations after the first and second doses were higher than those after the third and fourth doses. The Excel module, however, appeared accurate, suggesting that there may be a problem with the on-line conversion of the module. Further, addition of the extent of oral bioavailability to the Multiple Oral Dosing module will enhance the utility of this module.

Summary

Overall, the on-line pharmacokinetic simulation site is a very useful site for students in the introductory pharmacokinetics courses. Major advantages of the site over most of the other simulation programs are that only a web browser and internet access are required for the use of the modules (platform-independent) and the site may be used free of charge. Modifications of the modules as proposed above will improve the utility of the modules further.

Reviewed by Reza Mehvar, Ph.D.

Review Date - November 98

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