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Induction

Ind inputs

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

  1. 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.
  2. 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