De Graeve J, Van Cantfort J, Gilard P, Wermeille M M
Laboratoire de Chimie médicale, Centre Hospitalier Universitaire, Sart Tilman par Liège, Belgium.
Arzneimittelforschung. 1989 May;39(5):551-5.
The metabolic pathway of dimetindene (dimetindene maleate, Fenistil), an antiallergic drug commercially available for more than 20 years, has remained unknown. By means of HPLC, GC-MS and MS-MS, dimetindene was found to be hydroxylated on the indene moiety of the molecule both in vitro with hepatic microsomes of several species and in vivo in man. Cochromatographic analysis (HPLC and GC-MS) of the primary metabolites produced in vitro and in vivo demonstrated their similarities but revealed differences from the chemically synthesized 5-hydroxy-dimetindene. Using large volumes of in vitro incubations of rat microsomes with dimetindene and cofactors, 1.15 mg of pure primary metabolite were first produced and then extensively purified. The study of the NMR proton in one and two dimensions (COSY) clearly demonstrated that this metabolite is hydroxylated on the C6 of the indene moiety as compared to the C5 for the synthetic product.
马来酸氯苯那敏（Fenistil）是一种已上市20多年的抗过敏药物，其代谢途径一直不明。通过高效液相色谱（HPLC）、气相色谱 - 质谱联用（GC-MS）和串联质谱（MS-MS）分析发现，在多种物种的肝微粒体体外实验以及人体体内实验中，氯苯那敏分子茚部分均发生了羟基化反应。对体外和体内产生的主要代谢产物进行的共色谱分析（HPLC和GC-MS）表明它们具有相似性，但与化学合成的5-羟基氯苯那敏存在差异。利用大量大鼠微粒体与氯苯那敏及辅因子进行体外孵育，首次制备得到了1.15毫克纯的主要代谢产物，随后进行了广泛纯化。一维和二维核磁共振氢谱（COSY）研究清楚地表明，与合成产物的C5位羟基化相比，该代谢产物是茚部分的C6位发生了羟基化。
