Chu D T, Lico I M, Swanson R N, Marsh K C, Plattner J J, Pernet A G
Anti-infective Research Division, Abbott Laboratories, Abbott Park, IL 60064-3500.
Drugs Exp Clin Res. 1990;16(9):435-43.
Tosufloxacin (5, A-61827 tosylate or T-3262) is currently under product development by both Abbott Laboratories and Toyama Chemical Co. Its registration as antibacterial agent has been approved in Japan. It has been found to be extremely effective in treating several bacterial infections. However, due to its inherent low water solubility, the development of an intravenous formulation will be extremely difficult and may preclude its parenteral use. In search of a more water-soluble analog of tosufloxacin for parenteral use, the 3-formyl derivative of tosulfoxacin, A-71497 (13), was synthesized for evaluation. It was found to produce high plasma levels of tosufloxacin upon both oral and subcutaneous administration to mice. High plasma levels of tosufloxacin were also obtained when 13 was administered both orally and intravenously to dogs. It possesses increased water solubility and makes the development of intravenous formulation possible. The chemical synthesis as well as biological properties of A-71497 (13) are described.
妥舒沙星（5，A - 61827甲苯磺酸盐或T - 3262）目前正由雅培实验室和富山化学公司进行产品开发。它作为抗菌剂在日本已获注册批准。已发现它在治疗多种细菌感染方面极为有效。然而，由于其固有的低水溶性，开发静脉制剂将极为困难，可能会排除其肠胃外给药的用途。为了寻找一种更具水溶性的妥舒沙星类似物用于肠胃外给药，合成了妥舒沙星的3 - 甲酰基衍生物A - 71497（13）进行评估。发现对小鼠口服和皮下给药后，它能使血浆中妥舒沙星达到高浓度水平。对狗口服和静脉注射13后，也能获得血浆中妥舒沙星的高浓度水平。它具有增加的水溶性，使得开发静脉制剂成为可能。本文描述了A - 71497（13）的化学合成及其生物学特性。
