CYP2B6 基因变异对稳态时丁丙诺啡及其代谢物的血浆和尿液浓度的影响。
Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state.
机构信息
Department of Medicine, Bioengineering and Therapeutic Sciences, Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, California 94143-1220, USA.
出版信息
Pharmacogenet Genomics. 2013 Mar;23(3):135-41. doi: 10.1097/FPC.0b013e32835d9ab0.
BACKGROUND
Bupropion, an antidepressant and smoking cessation medication, is metabolized to hydroxybupropion (HB), an active metabolite, primarily by CYP2B6.
OBJECTIVES
To compare plasma concentrations of bupropion and metabolites at steady state in healthy volunteers with and without CYP2B6 genetic variants.
METHODS
In a genotype-guided study of 42 healthy individuals, we measured the plasma and urine concentrations of bupropion and its metabolites, HB, threohydrobupropion, and erythrohydrobupropion after 7 days of sustained-release bupropion dosing.
RESULTS
CYP2B6*6 and *18 gene variants were associated with ~33% reduced concentrations of HB, with no effects on concentrations of bupropion or other metabolites. We could account for 50% of the variation in HB concentrations in a model including genotype and sex.
CONCLUSION
As HB is active and its steady-state concentrations are more than 10 times higher than bupropion, CYP2B6 variants are likely to affect pharmacological activity. Because of the large individual variation within the genotype group, the use of therapeutic drug monitoring for dose optimization may be necessary.
背景
安非他酮是一种抗抑郁药和戒烟药物，其代谢产物羟基安非他酮（HB）是一种主要通过 CYP2B6 代谢的活性代谢物。
目的
比较有和无 CYP2B6 遗传变异的健康志愿者在稳态时的安非他酮及其代谢物血浆浓度。
方法
在一项 42 名健康个体的基因指导研究中，我们在持续 7 天给予安非他酮缓释剂后，测量了血浆和尿液中安非他酮及其代谢物 HB、 threohydrobupropion 和 erythrohydrobupropion 的浓度。
结果
CYP2B6*6 和 *18 基因突变与 HB 浓度降低约 33%相关，对安非他酮或其他代谢物浓度无影响。在包括基因型和性别在内的模型中，我们可以解释 HB 浓度变异的 50%。
结论
由于 HB 具有活性且其稳态浓度是安非他酮的 10 倍以上，因此 CYP2B6 变异可能会影响药理学活性。由于基因型组内个体差异较大，可能需要进行治疗药物监测以优化剂量。
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