Inhibition can be computed by two ways on Teoreler - Reversible and Time-dependent.
Reversible inhibition (competitive inhibition) 1, is given as follows:
where, Inhenz is fold inhibition of enzyme activity, Cdrugis concentration of the drug in the gut or liver (depending on where the equation is used), Ki is
the absolute inhibition constant and can be calculated using the equation below:
where I50 is concentration of inhibitor to inhibit 50% of an enzymatic reaction at a given substrate concentration, S is substrate concentration (in the gut or liver), K m is the Michaelis constant of the substrate.
In a time-dependent model, 2 rate of enzyme
degradation for a given enzyme is as follows:
where, dInhenz / dt is the change in fold inhibition of enzyme activity over time, kinact is maximal enzyme inactivation rate constant, Ki is inhibitor concentration at half maximal value of kinact.
- Yung-Chi C, Prusoff WH. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochemical Pharmacology. 1973 1973/12/01/;22(23):3099-108. https://doi.org/10.1016/0006-2952(73)90196-2.
- 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.