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}
}
  • K. A. KimW. SongJ. Park
  • Published 1 November 2009
  • Biology, Medicine, Chemistry
  • Clinical Pharmacology & Therapeutics
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… 
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Highly Influential Citations
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22 Citations

Effect of CYP2B6 Genotype on the Pharmacokinetics of Sibutramine and Active Metabolites in Healthy Subjects

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. PanS. Bae Jae-Gook Shin
  • Biology, Medicine
    Xenobiotica; the fate of foreign compounds in biological systems
  • 2013
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

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

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

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.

Enantioselective N-Demethylation and Hydroxylation of Sibutramine in Human Liver Microsomes and Recombinant Cytochrome P-450 Isoforms

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

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.

It is proposed that among Japan, Korea, and China, genetic differences are very small for the analyzed common PK-related gene polymorphisms.

An update on ethnic differences in drug metabolism and toxicity from anti-cancer drugs

This article reviews potential explanations for the observed ethnic differences in treatment outcomes and provides clinical data to support this concept and recommends that the development of new therapeutic agents should include patients from diverse geographical ancestries in each phase of drug development.

Which Metabolites Circulate ? s

This analysis suggests that fm is the major determinant of total drug M/P ratio for amine, alcohol, Nand S-oxide, and carboxylic acid metabolites and arenol metabolites show amore complex relationship with fm due largely to the new metabolic routes available to the metabolite compared with the parent drug molecule.

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