Introduction
"The effects of a
drug on the human body vary with many pharmacodynamic,
pharmacokinetic and administration parameters. These parameters
determine the concentration of the drug in the plasma and the
magnitude of its action over time. PharmSim offers the user a
chance to simulate these dynamic processes in an interactive way,
in order to obtain a better understanding of the interplay
between the different parameters and the importance of the dosing
regime on the effects of a drug.
The following
parameters are used:
- Half-maximal effective
drug concentration (EC50), the
drug concentration needed to achieve half of the maximal
effect
- Maximal drug effect (Emax), the maximal action that the drug can achieve.
In this simulation, Emax is
always 100% for simplicity..
- volume of distribution (Vd), calculated by dividing the total amount of
the drug in the body by the plasma concentration of the
drug
- oral availability (F), the
fraction of drug administered that reaches the central
circulation
- clearance (Cl), the volume
of plasma completely freed of drug per unit of time
- infusion rate (Ri), the amount of drug entering the body per unit
of time
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- dose (D), the amount of
drug administered at once
- dosing interval (T), the time between two administrations
- absorption rate constant (ka), a measure for the speed of
absorption
- toxic concentration (Ct), the minimal concentration of the drug that
causes toxicity
- upper time limit (tmax), the time span to be observed
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In addition, the user can
choose between the following modes of administration:
User manual for
PharmSim
- Operating PharmSim is extremely
easy. Click on the PharmSim link to get to the applet. On your
screen, you will see a number of text boxes, corresponding to the
different pharmacokinetic and pharmacodynamic parameters, and two
graphs, one for the plasma concentration over time and one for
the drug action over time. The textboxes are editable by simply
selecting the preset numbers and entering new values.
- The system requires numerical
input for the parameters needed for a specific calculation (see
the sections on formulas for more details on this matter). In
addition, the textboxes for the upper time limit and the toxic
comcentration always need to be filled. Also, make sure that the
input is given in the right units, as indicated after the
textboxes. If these conditions are met, the graphs will be drawn
after the user chosses a mode of administation by pressing the
corresponding button.
- The graphs that appear display
the course of the plasma concentration of the drug over time on
the left and the course of the relative drug action time on the
right. Since the values on the y-axis may vary significantly with
the different parameters, PharmSim autoscales the axis to the
maximal value of the graph. A new and extremely useful feature is
the waring that the toxic concentration is reached, by means of a
written warning and by changing the color of the concentration
graph red in the time intervals where the plasma concentration
exceeds the toxic concentration."
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Knowing this, you are ready to
run
This page and associated pharmacokinetic simulator pages, Copyright Thessa Kockelkorn,
May 2000, used with permission
