AI Article Synopsis
- The study investigates how different CYP2C19 genetic types affect the metabolism and effectiveness of the medication rabeprazole in healthy Chinese males after a single dose.
- Researchers analyzed plasma concentration and pH data to create a model showing that genetic variations influence the drug's clearance rates, with poor metabolizers (PM) showing the lowest clearance.
- Findings suggest that while the standard dose of rabeprazole may work for poor metabolizers, those with other genotypes might require more frequent dosing to effectively treat conditions like gastroesophageal reflux disease.
Article Abstract
Aims: To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach.
Methods: Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition.
Results: The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease.
Conclusion: The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.
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| http://dx.doi.org/10.1007/s00228-010-0892-4 | DOI Listing |
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