The US Food and Drug Administration (FDA) lists 22 medications as clinical inhibitors of cytochrome P450 2D6 isoenzyme, with classifications of strong, moderate, and weak. It is accepted that strong inhibitors result in nearly null enzymatic activity, but reduction caused by moderate and weak inhibitors is less well characterized. The objective was to identify if the classification of currently listed FDA moderate and weak inhibitors is supported by publicly available primary literature. We conducted a literature search and reviewed product labels for area under the plasma concentration‐time curve (AUC) fold‐changes caused by inhibitors in humans and identified 89 inhibitor–substrate pairs. Observed AUC fold‐change of the substrate was used to create an observed inhibitor classification per FDA‐defined AUC fold‐change thresholds. We then compared the observed inhibitor classification with the classification listed in the FDA Table of Inhibitors. We found 62% of the inhibitors within the pairs matched the listed FDA classification. We explored reasons for discordance and suggest modifications to the FDA table of clinical inhibitors for cimetidine, desvenlafaxine, and fluvoxamine.

中文翻译：

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细胞色素P450 2D6同工酶抑制剂分类背后证据的范围回顾。

美国食品药品监督管理局（FDA）列出了22种药物作为细胞色素P450 2D6同工酶的临床抑制剂，分类为强，中和弱。公认的是强抑制剂导致几乎没有酶活性，但是由中度和弱抑制剂引起的还原没有得到很好的表征。目的是确定可公开获得的主要文献是否支持当前列出的FDA中度和弱度抑制剂的分类。我们进行了文献检索并审查了产品标签中人体抑制剂引起的血浆浓度-时间曲线（AUC）倍数变化下面积，并确定了89种抑制剂-底物对。根据FDA定义的AUC倍数变化阈值，使用观察到的底物的AUC倍数变化创建观察到的抑制剂分类。然后，我们将观察到的抑制剂分类与FDA抑制剂表中列出的分类进行了比较。我们发现该对中的抑制剂中有62％符合列出的FDA分类。我们探讨了不一致的原因，并建议修改FDA的西咪替丁，去甲文拉法辛和氟伏沙明临床抑制剂表。