CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial

Anna M. Lee, Christopher Jepson, Ewa Hoffmann, Leonard Epstein, Larry W. Hawk, Caryn Lerman, Rachel F. Tyndale

Research output: Contribution to journalArticle

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Abstract

Background: CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome. Methods: Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants. Results: Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98-9.06, p = .05). Conclusions: These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.

Original languageEnglish (US)
Pages (from-to)635-641
Number of pages7
JournalBiological Psychiatry
Volume62
Issue number6
DOIs
StatePublished - Sep 15 2007

Fingerprint

Bupropion
Smoking Cessation
Genotype
Placebos
Therapeutics
Odds Ratio
Cytochrome P-450 CYP2B6
Confidence Intervals
Genetic Polymorphisms
Smoke
Clinical Trials

Keywords

  • Bupropion
  • CYP2A6
  • CYP2B6
  • genetic
  • nicotine
  • pharmacogenetic
  • smoking

Cite this

Lee, A. M., Jepson, C., Hoffmann, E., Epstein, L., Hawk, L. W., Lerman, C., & Tyndale, R. F. (2007). CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial. Biological Psychiatry, 62(6), 635-641. https://doi.org/10.1016/j.biopsych.2006.10.005

CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial. / Lee, Anna M.; Jepson, Christopher; Hoffmann, Ewa; Epstein, Leonard; Hawk, Larry W.; Lerman, Caryn; Tyndale, Rachel F.

In: Biological Psychiatry, Vol. 62, No. 6, 15.09.2007, p. 635-641.

Research output: Contribution to journalArticle

Lee, AM, Jepson, C, Hoffmann, E, Epstein, L, Hawk, LW, Lerman, C & Tyndale, RF 2007, 'CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial', Biological Psychiatry, vol. 62, no. 6, pp. 635-641. https://doi.org/10.1016/j.biopsych.2006.10.005
Lee, Anna M. ; Jepson, Christopher ; Hoffmann, Ewa ; Epstein, Leonard ; Hawk, Larry W. ; Lerman, Caryn ; Tyndale, Rachel F. / CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial. In: Biological Psychiatry. 2007 ; Vol. 62, No. 6. pp. 635-641.
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abstract = "Background: CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome. Methods: Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants. Results: Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45{\%} of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5{\%} vs. 14.3{\%}, p = .01) and at the 6-month follow-up (31.2{\%} vs. 12.9{\%}, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0{\%} vs. 31.6{\%}, p = .93) or at the 6-month follow-up (22.0{\%} vs. 21.5{\%}, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98-9.06, p = .05). Conclusions: These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.",
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T1 - CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial

AU - Lee, Anna M.

AU - Jepson, Christopher

AU - Hoffmann, Ewa

AU - Epstein, Leonard

AU - Hawk, Larry W.

AU - Lerman, Caryn

AU - Tyndale, Rachel F.

PY - 2007/9/15

Y1 - 2007/9/15

N2 - Background: CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome. Methods: Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants. Results: Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98-9.06, p = .05). Conclusions: These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.

AB - Background: CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome. Methods: Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants. Results: Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98-9.06, p = .05). Conclusions: These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.

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KW - nicotine

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