Editor-in-Chief
Hatice Kübra Elçioğlu
Vice Editors
Levent Kabasakal
Esra Tatar
Online ISSN
2630-6344
Publisher
Marmara University
Frequency
Bimonthly (Six issues / year)
Abbreviation
J.Res.Pharm.
Former Name
Marmara Pharmaceutical Journal
Journal of Research in Pharmacy
2023 , Vol 27 , Issue Supp.
PHARMAKOKINETIC EVALUATION WITH SIMCYP PROGRAM
1Pharmacotherapeutic Research Center, Faculty of Medical Sciences, Aldent University, Tirana, Albania2Department of Pharmacy, Faculty of Medicine, University of Medicine, Tirana, Albania
3Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, the Netherlands
4Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands DOI : 10.29228/jrp.453 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