Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition.
Clin Pharmacol Ther
; 105(1): 142-152, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-29756345
ABSTRACT
Bupropion hydroxylation is a bioactivation and metabolic pathway, and the standard clinical CYP2B6 probe. This investigation determined the influence of CYP2B6 allelic variants on clinical concentrations and metabolism of bupropion enantiomers. Secondary objectives evaluated the influence of CYP2C19 and P450 oxidoreductase variants. Healthy volunteers in specific cohorts (CYP2B6*1/*1, CYP2B6*1/*6, CYP2B6*6/*6, and also CYP2B6*4 carriers) received single-dose oral bupropion. Plasma and urine bupropion and hydroxybupropion was quantified. Subjects were also genotyped for CYP2C19 and P450 oxidoreductase variants. Hydroxylation of both bupropion enantiomers, assessed by plasma hydroxybupropion/bupropion AUC ratios and urine hydroxybupropion formation clearances, was lower in CYP2B6*6/*6 but not CYP2B6*1/*6 compared with CYP2B6*1/*1 genotypes, and numerically greater in CYP2B6*4 carriers. CYP2C19 and P450 oxidoreductase variants did not influence bupropion enantiomers hydroxylation or plasma concentrations. The results show that clinical hydroxylation of both bupropion enantiomers was equivalently influenced by CYP2B6 allelic variation. CYP2B6 polymorphisms affect S-bupropion bioactivation, which may affect therapeutic outcomes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bupropiona
/
Antidepressivos de Segunda Geração
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Polimorfismo de Nucleotídeo Único
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Citocromo P-450 CYP2B6
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos