Kaixi Cui
ABSTRACT
Drug safety and efficacy have found to be highly variable among patients with different ages, gender, genetics and so on. The genetic polymorphisms in different individuals are one of the major components. Meclizine is an antihistamine used to prevent and treat motion sickness. CYP2D6 has been identified to be the main subtype for meclizine metabolism. However, the effect of CYP2D6 genotypes on meclizine pharmacokinetics has not been investigated. In this study, a physiologically based pharmacokinetic model focusing on the metabolism of meclizine was established and used to predict the pharmacokinetics of meclizine in human subjects with different CYP2D6 genotypes. The initial estimation of the pharmacokinetic parameters was calculated using the reported data. The clearance of meclizine was predicted based on the in vitro microsome studies. Other physicochemical properties of meclizine were determined or predicted in this study. The results showed our model can reasonably fit the data. In addition, the CYP2D6 *5/*5 could lead to significantly higher plasma concentrations. In conclusion, this study predicted the potential impact of CYP2D6 genotypes on the meclizine pharmacokinetics, although further study needs to be conducted to verify the simulation results.
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Index Terms
- Predicting the Impact of CYP2D6 Genetic Polymorphisms on Meclizine Pharmacokinetics and Pharmacodynamics
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