PHARMAKOKINETIC EVALUATION WITH SIMCYP PROGRAM

Year 2023, Volume: 27 Issue: Current Research Topics In Pharmacy: In silico Approaches for Drug Design and Discovery, 4 - 5, 28.06.2025

Enkelejda Goci Joyce Van Der Heijden Saskia De Wildt

https://doi.org/10.29228/jrp.453

https://izlik.org/JA97CG36UD

Abstract

The anticonvulsant carbamazepine is a first-line drug in the treatment of most forms of epilepsy and also the drug of first choice in trigeminal neuralgia. It is a known substrate and inducer of cytochrome P450 (CYP) 3A4 and CYP2B6. Carbamazepine induces the metabolism of various drugs (including its own); on the other hand, its metabolism can be affected by various CYP inhibitors and inducers. The aim of this work was to develop a physiologically based pharmacokinetic (PBPK) model of carbamazepine dosing in pediatrics by using Simcyp Simulator platform. The model is based in vivo pharmacokinetic data and verified using an independent set of published clinical pharmacokinetic data in adult and pediatric population. The PK data observed and predicted were compared and evaluated, by visual predictive check [1-3]. The major enzyme in carbamazepine metabolism is CYP3A4 that, according to Simcyp, its activity increases with 2-fold. CL is more accurately predicted in multi-dose simulations compared to single-dose simulations. Moreover, pediatric predictions are very accurate, including the CL [1-3]. Overall, the adult multi-dose predictions are better than adult single-dose. Paediatric exposure is accurately predicted. Thus, the paediatric multi-dose carbamazepine exposure can be simulated by Simcyp. When the simulation results are combined with the pharmacodynamics of carbamazepine, dosing recommendations may be suggested [1-3].

Keywords

Carbamazepine , Simcyp , PBPK model , Pharmacokinetic

References

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