Contents
Get started Distribution Method validation Interactive comparison Poulin and Theil Berezhkovskiy L. M. Rodgers and Rowland Schmitt W PK-Sim® Schmitt et al. 2020
Induction Inhibition Elimination Dosing inputs Sex Population Age range Strain Dose Interval Repeats End time Simulation time Time units
Upload data Download data ReferencesInduction

Induction can be computed by two ways on Teoreler - using Static and Indirect effect models.
In a static model1,2, fold induction of an enzyme
is computed as follows:
Indenz = 1 + (Emax ×
Cdrug)/(EC50 + Cdrug) [ 1 ]
where, Indenz is fold-induction of enzyme activity, Emax is maximal activation in vitro, EC50 is concentration of the inducer at half maximal response and Cdrug is concentration of the drug in the gut or liver (depending on where the equation is used) at a given time.
In an indirect effect model, 2 rate of synthesis
and
sequestration of enzymes are also included as follows:
dIndenz / dt = kdeg (1 + (Emax ×
Cdrug)/(EC50 + Cdrug) - Indenz) [ 2 ]
where, dIndenz / dt is change in fold induction of enzyme activity over time and kdeg is enzyme degradation rate constant (h⁻¹).
References
- Evaluation of Drug–Drug Interaction Risk with PBPK Models. Physiologically‐Based Pharmacokinetic (PBPK) Modeling and Simulations; 2012. p.183-207.https://doi.org/10.1002/9781118140291.ch9.
- Yamashita F, Sasa Y, Yoshida S, Hisaka A, Asai Y, Kitano H, et al. Modeling of rifampicin-induced CYP3A4 activation dynamics for the prediction of clinical drug-drug interactions from in vitro data. PLoS One. 2013;8(9):e70330. https://doi.org/10.1371/journal.pone.0070330