Association of CYP2B6, CYP3A5, and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects

@article{Kim2009AssociationOC,
  title={Association of CYP2B6, CYP3A5, and CYP2C19 Genetic Polymorphisms With Sibutramine Pharmacokinetics in Healthy Korean Subjects},
  author={K A Kim and W K Song and J. Y. Park},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2009},
  volume={86}
}
We assessed the association of CYP2B6, CYP3A5, and CYP2C19 polymorphisms with sibutramine pharmacokinetics. Forty six healthy male subjects were enrolled, and their CYP2B6 (*4 and *6), CYP3A5 (*3), and CYP2C19 (*2, and *3) genotypes were analyzed. After a single 15‐mg dose of sibutramine was administered, plasma concentrations of sibutramine and its metabolites, M1 and M2, were measured. CYP2B6 and CYP3A5 polymorphisms did not affect the pharmacokinetics of sibutramine and its metabolites… 
Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy: a crucial role for the CYP2B6*6 allele.
TLDR
The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment, and is significant only among the CYP 2B6 genotypes.
Effect of CYP2B6 Genotype on the Pharmacokinetics of Sibutramine and Active Metabolites in Healthy Subjects
TLDR
The CYP2B6*6 allele may be associated with a lower metabolic clearance of the M1 metabolite of sibutramine in human subjects.
Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6*6 polymorphism
  • W. Pan, S. Bae, +7 authors Jae-Gook Shin
  • Chemistry, Medicine
    Xenobiotica; the fate of foreign compounds in biological systems
  • 2013
TLDR
The results suggest that the perturbation of CYP2B6 activity may contribute to the inter-individual variation of sibutramine drug responses although the clinical relevance is remained to be established.
Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers
TLDR
The results indicated that the genetic polymorphism of CYP3A5*3 but not ABCB1 significantly influences the plasma level of quetiapine and its pharmacokinetics and provide a plausible explanation for interindividual variation in the disposition of this drug.
Effects of Clopidogrel on the Pharmacokinetics of Sibutramine and Its Active Metabolites
TLDR
CYP2B6 and CYP2C19 are in vivo catalysts for the formation of the 2 active metabolites of sibutramine and clopidogrel significantly increased the half‐life and area under the plasma concentration—time curve from 0 to infinity (AUCinf) and decreased the apparent oral clearance (31% of control phase).
Different Effects of Clopidogrel and Clarithromycin on the Enantioselective Pharmacokinetics of Sibutramine and its Active Metabolites in Healthy Subjects
TLDR
The results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo.
Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype–phenotype correlation in childhood
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According to the results from a Turkish pediatric population, lansoprazole is a suitable probe drug for phenotyping CYP2C19 and the CYP 2C19*2 and *17 variants should be taken into consideration in predicting the clinical outcome of therapy with lansopsine in the pediatric population.
Enantioselective N-Demethylation and Hydroxylation of Sibutramine in Human Liver Microsomes and Recombinant Cytochrome P-450 Isoforms
TLDR
It is indicated that S-sibutramine was more rapidly metabolized by CYP isoforms than R-sibiaetramine, and that enantioselective metabolism needs to be considered in drug interactions involving sibutramsine and co-administered drugs.
In Vivo Quantitative Prediction of the Effect of Gene Polymorphisms and Drug Interactions on Drug Exposure for CYP2C19 Substrates
TLDR
This study shows that pharmacogenetic information can be used to predict DDI, which may have important implications for the development of personalized medicine and drug development.
Population differences in major functional polymorphisms of pharmacokinetics/pharmacodynamics-related genes in Eastern Asians and Europeans: implications in the clinical trials for novel drug development.
TLDR
It is proposed that among Japan, Korea, and China, genetic differences are very small for the analyzed common PK-related gene polymorphisms.
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