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Clin Chim Acta. 2014 Jan 20;428:77-81. doi: 10.1016/j.cca.2013.11.007. Epub 2013 Nov 19.

Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy: a crucial role for the CYP2B6*6 allele.

Author information

1
Department of Family Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
2
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, South Korea. Electronic address: jypark21@korea.ac.kr.
3
Department of Statistics, Dongguk University, Seoul, South Korea.
4
Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, South Korea.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01184560.

KEYWORDS:

CYP2B6; Polymorphisms; Sibutramine

PMID:
24262967
DOI:
10.1016/j.cca.2013.11.007
[Indexed for MEDLINE]
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