Tutorial for PharmaCalc
Simulate plasma-concentration time curves
PharmaCalc v02 is an educational tool that allows to simulate plasma-concentration time curves based on chosen pharmacokinetic parameters.
It should help to better understand
- the influence of the pharmacokinetic parameters on plasma-concentration time curves
- the effects of changing a dosing interval (e.g., missing a dose) or changing a dose or both
- the influence of a loading dose.
How this tool will help: Think about the effects any (change in) parameter(s), dose or interval will have on the plasma-concentration time curve of a drug. Calculate the total clearance (CL) the maximal (peak) concentration at stady state for multiple dosing (Css,max,i.v.), and a hypothetical loading dose to reach Css,max,i.v. with the first dose. Then find out with a few entries and a click whether your expectations were correct.
You may start as follows:
- Choose whether you would like to use a drug from the library or whether you prefer to enter pharmacokinetic parameters manually: Use the uppermost pull-down choice to choose a pharmacokinetic model (1-compartment, 2-compartments, intravascular, extravascular, infusion) or use the choice below to choose a drug from the library.
- Selecting a drug from the library will enter the parameters automatically. In case you chose the manual entry, select the model and enter the pharmacokinetic parameters manually.
- Now click on the green button "Draw curve, calculate above params". Two windows will open with the plasma-concentration time curve calculated with the parameters in the parameter entry panel. The upper graph shows the lin-lin-plot, the lower one the ln (natural logarithm)-lin plot.
- The therapeutic window is indicated by the two horizontal lines in the plots unless the respective entries were zero (two fields in the parameter entry panel). You may enter your own values for the therapeutic window. Note, plots are only redrawn upon clicking the green "Draw curve, ..." button.
- By clicking the green button, Css,av,i.v., CL and the hypothetical loading dose were in addition calculated from the entered parameters.
- Next, click the button "Propagate interval and dose from above to 2.-24. dose". This will copy the entries from "Subsequent doses (mg)" and "General interval (h)" to the 2. - 24. doses below.
- Click the green button again and the plots now show the curve over the 24 doses, including 7 half life times after the last dose. Note that pervious plots are still there, hidden by the new plots. Close plots from time to time when not used anymore.
- Now, change one or several of the intervals, e.g., assuming one, two, three doses were missed. Double, half a dose etc. and think how the curve will change.
- Or change half life to simulate a poor or ultra rapid metabolizer or to simulate enzyme inhibition or induction.
- Click the green button again and verify your expectations.
- You can apply the hypothetical loading dose by clicking "Apply hypothetical loading dose". This will copy the calculated hypothetical loading dose to the respective field above on the right. Alternatively, enter your own choice of loading dose directly to the right upper field. This field will turn yellow if different from subsequent doses after clicking the green button. See the effect on the plasma-concentration time curve in the plots. This loading dose is called hypothetical here, as it may be too high for a single dose.
- The slider "Resolution in time" will change the step size of the drawn curves. Note that calculation time increases with decreasing step size (sliding to the right).
- The "Example" button calls a drug from the library (author's choice).
All calculations are based on
- P. Langguth, G. Fricker, H. Wunderli-Allenspach. Biopharmazie. Wiley-VCH, Weinheim, 2004.
- M. Rowland, T.N. Tozer. Clinical Pharmacokinetics and Pharmacodynamics - Concepts and Applications. Fourth edition. Wolters Kluwer / Lippincott, Baltimore / Philadelphia, 2011.
Parameters in the drug library are from various sources and may be incorrect or may apply to only part of a population. Individual variabilities are not taken into account in this tool.