Williams M L, Wainer I W
Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA.
Curr Pharm Des. 1999 Aug;5(8):665-72.
Ifosfamide and cyclophosphamide are alkylating agents that are extensively used in the clinical treatment of cancer. However, the continued use of ifosfamide has been questioned with the suggestion that cyclophosphamide be used exclusively. One response to this proposal is based upon the fact that both cyclophosphamide and isfosfamide are chiral and are administered as racemic (50:50) mixtures of the two isomers. Studies of the clinical pharmacology, metabolism and disposition of these agents indicate that stereochemistry plays a minor role in the efficacy and toxicity of cyclophosphamide but is a major factor in neurotoxicity associated with ifosfamide administration. Studies have demonstrated that the use of a single ifosfamide enantiomer, (R)-ifosfamide would retain the unique antitumor efficacy of this agent, while eliminating the major source of the observed ifosfamide-associated neurotoxicity, (S)-ifosfamide.
异环磷酰胺和环磷酰胺是广泛用于癌症临床治疗的烷化剂。然而，异环磷酰胺的持续使用受到了质疑，有人建议仅使用环磷酰胺。对此提议的一种回应基于这样一个事实，即环磷酰胺和异环磷酰胺都是手性的，并且以两种异构体的外消旋（50:50）混合物形式给药。对这些药物的临床药理学、代谢和处置的研究表明，立体化学在环磷酰胺的疗效和毒性中起次要作用，但在与异环磷酰胺给药相关的神经毒性中是一个主要因素。研究表明，使用单一的异环磷酰胺对映体，即（R）-异环磷酰胺，将保留该药物独特的抗肿瘤疗效，同时消除观察到的与异环磷酰胺相关的神经毒性的主要来源，即（S）-异环磷酰胺。
