title: Effects of CYP3A5, CYP2C19, and CYP2B6 on the clinical efficacy and adverse outcomes of sibutramine therapy: a crucial role for the CYP2B6*6 allele.
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).
  
  
  CONCLUSIONS
  The CYP2B6*6 allele influences the extent of weight reduction and pulse rate changes in patients undergoing sibutramine treatment.
authors.affiliation: Department of Family Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: In Cheol
authors.initials: IC
authors.lastname: Hwang
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, South Korea. Electronic address: jypark21@korea.ac.kr.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Statistics, Dongguk University, Seoul, South Korea.
authors.forename: Hong Yup
authors.initials: HY
authors.lastname: Ahn
authors.affiliation: Department of Family Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: Kyoung Kon
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Department of Family Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: Heuy Sun
authors.initials: HS
authors.lastname: Suh
authors.affiliation: Department of Family Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: Ki Dong
authors.initials: KD
authors.lastname: Ko
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Kyoung-Ah
authors.initials: KA
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D003503:Cyclobutanes / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics* / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D000077403:Orlistat; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D011674:Pulse; D012044:Regression Analysis; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
chemical_list: D003503:Cyclobutanes; D007783:Lactones; D000077403:Orlistat; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C058254:sibutramine
keywords: CYP2B6; Polymorphisms; Sibutramine