Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy

A crucial role for the CYP2B6*6 allele

In Cheol Hwang, Ji-Young Park, Hong Yup Ahn, Kyoung Kon Kim, Heuy Sun Suh, Ki Dong Ko, Kyoung Ah Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Various cytochrome P450 isoforms modulate sibutramine activity and influence sibutramine plasma levels and pharmacokinetics. However, there are no available data to demonstrate the association of these polymorphisms with the clinical outcomes of sibutramine administration. Methods: This study was a sub-investigation of a 12-week, double-blind, placebo-controlled trial examining the additive effect of orlistat on sibutramine. The final analysis was restricted to 101 women who had fulfilled the protocol. We evaluated the effects of genetic polymorphisms of CYP3A5, CYP2C19 and CYP2B6 on the % weight loss and the occurrence of adverse events. Results: The change of pulse rate from baseline value was affected by both CYP2B6 and CYP3A5 genetic polymorphisms (P < .01 for CYP3A5 and P = .01 for CYP2B6). Both CYP2B6 and CYP3A5 showed gene-gene interactions (P < .01). After adjusting for significant variables in the backward stepwise regression model, the change of pulse rate and time-dependent weight reduction were significant only among the CYP2B6 genotypes (P = .027 and P < .01, respectively). Conclusion: The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment.

Original languageEnglish
Pages (from-to)77-81
Number of pages5
JournalClinica Chimica Acta
Volume428
DOIs
Publication statusPublished - 2014 Jan 20

Fingerprint

sibutramine
Cytochrome P-450 CYP3A
Alleles
Polymorphism
Weight Loss
Heart Rate
Genetic Polymorphisms
Therapeutics
Genes
Pharmacokinetics
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2B6
Protein Isoforms
Genotype
Placebos

Keywords

  • CYP2B6
  • Polymorphisms
  • Sibutramine

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy : A crucial role for the CYP2B6*6 allele. / Hwang, In Cheol; Park, Ji-Young; Ahn, Hong Yup; Kim, Kyoung Kon; Suh, Heuy Sun; Ko, Ki Dong; Kim, Kyoung Ah.

In: Clinica Chimica Acta, Vol. 428, 20.01.2014, p. 77-81.

Research output: Contribution to journalArticle

Hwang, In Cheol ; Park, Ji-Young ; Ahn, Hong Yup ; Kim, Kyoung Kon ; Suh, Heuy Sun ; Ko, Ki Dong ; Kim, Kyoung Ah. / Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy : A crucial role for the CYP2B6*6 allele. In: Clinica Chimica Acta. 2014 ; Vol. 428. pp. 77-81.
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abstract = "Background: Various cytochrome P450 isoforms modulate sibutramine activity and influence sibutramine plasma levels and pharmacokinetics. However, there are no available data to demonstrate the association of these polymorphisms with the clinical outcomes of sibutramine administration. Methods: This study was a sub-investigation of a 12-week, double-blind, placebo-controlled trial examining the additive effect of orlistat on sibutramine. The final analysis was restricted to 101 women who had fulfilled the protocol. We evaluated the effects of genetic polymorphisms of CYP3A5, CYP2C19 and CYP2B6 on the {\%} weight loss and the occurrence of adverse events. Results: The change of pulse rate from baseline value was affected by both CYP2B6 and CYP3A5 genetic polymorphisms (P < .01 for CYP3A5 and P = .01 for CYP2B6). Both CYP2B6 and CYP3A5 showed gene-gene interactions (P < .01). After adjusting for significant variables in the backward stepwise regression model, the change of pulse rate and time-dependent weight reduction were significant only among the CYP2B6 genotypes (P = .027 and P < .01, respectively). Conclusion: The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment.",
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AU - Park, Ji-Young

AU - Ahn, Hong Yup

AU - Kim, Kyoung Kon

AU - Suh, Heuy Sun

AU - Ko, Ki Dong

AU - Kim, Kyoung Ah

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N2 - Background: Various cytochrome P450 isoforms modulate sibutramine activity and influence sibutramine plasma levels and pharmacokinetics. However, there are no available data to demonstrate the association of these polymorphisms with the clinical outcomes of sibutramine administration. Methods: This study was a sub-investigation of a 12-week, double-blind, placebo-controlled trial examining the additive effect of orlistat on sibutramine. The final analysis was restricted to 101 women who had fulfilled the protocol. We evaluated the effects of genetic polymorphisms of CYP3A5, CYP2C19 and CYP2B6 on the % weight loss and the occurrence of adverse events. Results: The change of pulse rate from baseline value was affected by both CYP2B6 and CYP3A5 genetic polymorphisms (P < .01 for CYP3A5 and P = .01 for CYP2B6). Both CYP2B6 and CYP3A5 showed gene-gene interactions (P < .01). After adjusting for significant variables in the backward stepwise regression model, the change of pulse rate and time-dependent weight reduction were significant only among the CYP2B6 genotypes (P = .027 and P < .01, respectively). Conclusion: The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment.

AB - Background: Various cytochrome P450 isoforms modulate sibutramine activity and influence sibutramine plasma levels and pharmacokinetics. However, there are no available data to demonstrate the association of these polymorphisms with the clinical outcomes of sibutramine administration. Methods: This study was a sub-investigation of a 12-week, double-blind, placebo-controlled trial examining the additive effect of orlistat on sibutramine. The final analysis was restricted to 101 women who had fulfilled the protocol. We evaluated the effects of genetic polymorphisms of CYP3A5, CYP2C19 and CYP2B6 on the % weight loss and the occurrence of adverse events. Results: The change of pulse rate from baseline value was affected by both CYP2B6 and CYP3A5 genetic polymorphisms (P < .01 for CYP3A5 and P = .01 for CYP2B6). Both CYP2B6 and CYP3A5 showed gene-gene interactions (P < .01). After adjusting for significant variables in the backward stepwise regression model, the change of pulse rate and time-dependent weight reduction were significant only among the CYP2B6 genotypes (P = .027 and P < .01, respectively). Conclusion: The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment.

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