Valotis Anagnostis, Neukam Konrad, Elert Olaf, Högger Petra
Institut für Pharmazie und Lebensmittelchemie, Bayerische Julius-Maximilians-Universität, Am Hubland, 97074 Würzburg, Germany.
J Pharm Sci. 2004 May;93(5):1337-50. doi: 10.1002/jps.20049.
Mometasone furoate (MF) is a topically used glucocorticoid with high anti-inflammatory potency. In contrast to the wealth of data derived from clinical studies, information about the molecular pharmacology of the compound is lacking or contradictory. Thus, we elucidated the characteristics of receptor binding kinetics and receptor affinity in a bioassay. Metabolite formation was determined in human plasma and lung tissue as well as binding affinity to human lung tissue. Fast and extensive association of MF to the human glucocorticoid receptor was observed while the dissociation of the MF-receptor complex was faster compared to fluticasone propionate (FP). The relative receptor affinity of MF was calculated as 2200 (dexamethasone = 100, FP = 1800) and confirmed in a bioassay measuring the induction of the glucocorticoid regulated protein CD163 in human monocytes. In plasma and human lung tissue MF formed a 9,11-epoxy degradation product. The binding affinity of MF to human lung tissue was low compared to FP due to fast redistribution from tissue into plasma. These molecular pharmacological properties are in accordance with clinical data.
糠酸莫米松（MF）是一种局部使用的具有高抗炎效力的糖皮质激素。与来自临床研究的大量数据相比，关于该化合物分子药理学的信息缺乏或相互矛盾。因此，我们在生物测定中阐明了受体结合动力学和受体亲和力的特征。在人血浆和肺组织中测定了代谢物形成以及与人肺组织的结合亲和力。观察到MF与人糖皮质激素受体的快速且广泛结合，而与丙酸氟替卡松（FP）相比，MF-受体复合物的解离更快。MF的相对受体亲和力经计算为2200（地塞米松=100，FP=1800），并在测量人单核细胞中糖皮质激素调节蛋白CD163诱导的生物测定中得到证实。在血浆和人肺组织中，MF形成了一种9,11-环氧降解产物。由于从组织到血浆的快速再分布，MF与人肺组织的结合亲和力低于FP。这些分子药理学特性与临床数据相符。
