人体肾上腺作为药物代谢器：甾体药物转化的首例体内证据。
The human adrenal gland as a drug metabolizer: First in-vivo evidence for the conversion of steroidal drugs.
机构信息
Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics in Paediatric Endocrinology, Division of Paediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
出版信息
J Steroid Biochem Mol Biol. 2019 Nov;194:105438. doi: 10.1016/j.jsbmb.2019.105438. Epub 2019 Jul 27.
The metabolism of drugs in mammals is attributed mainly to the liver and its cytochromes P450 localized in the endoplasmic reticulum. Here, we demonstrate for the first time in humans that there is no strict subdivision between P450 s involved in exogenous and endogenous metabolism. We determined the widely used mineralocorticoid receptor antagonist spironolactone, its active metabolite canrenone and their metabolites in the adrenal venous blood of treated patients with gas chromatography-mass spectrometry. 11- and 18-hydroxylated metabolites of canrenone were found in the efferent right and left adrenal veins, indicating that they were produced by the adrenal mitochondrial cytochromes P450 CYP11B1 and CYP11B2. Thus, the adrenal has to be considered as a new organ for drug metabolism. In future, application of drugs may need further investigations concerning side effects due to interactions with adrenal enzymes.
哺乳动物的药物代谢主要归因于肝脏及其内质网中的细胞色素 P450。在这里，我们首次在人体中证明，参与外源性和内源性代谢的 P450 之间没有严格的细分。我们使用气相色谱-质谱法在接受治疗的患者的肾上腺静脉血中测定了广泛使用的盐皮质激素受体拮抗剂螺内酯、其活性代谢产物坎利酮及其代谢物。在右和左肾上腺静脉的流出液中发现了坎利酮的 11-和 18-羟化物，表明它们是由肾上腺线粒体细胞色素 P450 CYP11B1 和 CYP11B2 产生的。因此，肾上腺必须被视为一个新的药物代谢器官。在未来，由于与肾上腺酶的相互作用，药物的应用可能需要进一步研究其副作用。
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