Cassatt David R, Fazenbaker Christine A, Kifle Gizachew, Bachy Christine M
Department of Molecular Biology/Biochemistry, MedImmune, Inc., Gaithersburg, MD 20872, USA.
Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):794-802. doi: 10.1016/s0360-3016(03)00660-6.
Amifostine (Ethyol) is currently approved for intravenous (IV) administration to prevent xerostomia in patients receiving radiotherapy for head-and-neck cancer. Recently, subcutaneous (SC) administration has been explored as an alternative route. To determine whether SC administration was equivalent to IV administration, we used models to follow pharmacokinetics and oral mucosal protection in rats.
Amifostine was administered to rats at doses of 200, 100, or 50 mg/kg (1300, 650, or 325 mg/m(2)) IV or SC at various times before radiation at 15.3 Gy (protection studies) or harvest of blood and tissues for analysis by HPLC (pharmacokinetic studies).
Amifostine administered IV or SC 1 h before radiation protected rats from mucositis, but the protective effect was more prolonged when amifostine was administered SC. Tissue levels of the active metabolite (WR-1065) were equivalent after SC administration. The correlation between tissue levels of WR-1065 and protection was strong, but that between blood levels of WR-1065 and protection was only weak.
These data demonstrate that, in a rat model, SC administration of amifostine was at least as effective as that by IV.
氨磷汀（依硫醇）目前已获批静脉注射给药，用于预防接受头颈癌放疗患者的口腔干燥症。最近，已探索皮下注射作为一种替代给药途径。为确定皮下注射是否等同于静脉注射，我们使用模型追踪大鼠的药代动力学和口腔黏膜保护情况。
在大鼠接受15.3 Gy辐射前的不同时间，以200、100或50 mg/kg（1300、650或325 mg/m²）的剂量静脉注射或皮下注射氨磷汀（进行保护研究），或采集血液和组织用于高效液相色谱分析（进行药代动力学研究）。
在辐射前1小时静脉注射或皮下注射氨磷汀可保护大鼠免受黏膜炎影响，但皮下注射氨磷汀时保护作用持续时间更长。皮下注射后活性代谢物（WR - 1065）的组织水平相当。WR - 1065的组织水平与保护作用之间相关性很强，但WR - 1065的血液水平与保护作用之间相关性较弱。
这些数据表明，在大鼠模型中，皮下注射氨磷汀至少与静脉注射一样有效。
