tailieunhanh - Báo cáo y học: " Significant receptor affinities of metabolites and a degradation product of mometasone furoate"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: " Significant receptor affinities of metabolites and a degradation product of mometasone furoate. | Respiratory Research BioMed Central Research Open Access Significant receptor affinities of metabolites and a degradation product of mometasone furoate Anagnostis Valotis and Petra Hogger Address Institut fur Pharmazie und Lebensmittelchemie Bayerische Julius-Maximilians-Universitat Wurzburg Germany Email Anagnostis Valotis - valotis@ Petra Hogger - hogger@ Corresponding author Published 22 July 2004 Received 05 February 2004 Respiratory Research 2004 5 7 doi 1465-9921-5-7 Accepted 22 July 2004 This article is available from http content 5 1 7 2004 Valotis and Hogger licensee BioMed Central Ltd. This is an open-access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Mometasone furoate MF is a highly potent glucocorticoid used topically to treat inflammation in the lung nose and on the skin. However so far no information has been published on the human glucocorticoid receptor activity of the metabolites or degradation products of MF. We have now determined the relative receptor binding affinities of the known metabolite 6P-OH MF and the degradation product 9 1 I-epoxy MF to understand their possible contribution to undesirable systemic side effects. In competition experiments with human lung glucocorticoid receptors we have determined the relative receptor affinities RRA of these substances with reference to dexamethasone RRA I00 . We have discovered that 6P-OH MF and 9 II-epoxy MF display RRAs of 206 15 and 220 22 respectively. This level of activity is similar to that of the clinically used inhaled corticosteroid flunisolide RRA I80 II . Furthermore we observed that 9 II-epoxy MF is a chemically reactive metabolite. In recovery experiments with human plasma and lung tissue we found a time .