McLoon L K, Josephson K, Wirtschafter J
University of Minnesota, Department of Ophthalmology, Minneapolis 55455, USA.
Curr Eye Res. 1999 Sep;19(3):285-9. doi: 10.1076/ceyr.19.3.285.5311.
An experimental treatment for benign essential blepharospasm and hemifacial spasm involves the direct injection of doxorubicin into the eyelids to permanently kill muscle. This study examined the extent of local and systemic spread of doxorubicin after localized injections of low doses into the eyelid and determined the length of time doxorubicin was retained in the eyelid after injection.
Two mg doxorubicin was injected subcutaneously into the lower eyelids of rabbits. After various time periods, the eyelids were removed and dissected into three separate specimens consisting of skin, subcutaneous connective tissue including orbicularis oculi muscle, or palpebral conjunctiva. Nearby tissues were also collected, including facial muscles and extraocular muscles. Urine, blood, kidney, spleen, heart and liver samples were collected. All tissues were prepared for HPLC determination of doxorubicin concentration.
Doxorubicin was detected in all three eyelid specimens for the first 4 days after injection, although by the fourth day the level of doxorubicin was greatly reduced. On and after the seventh day, there was no detectable doxorubicin in the treated eyelid tissues. There were no detectable levels of doxorubicin in the urine or any other body tissue at any of the post-injection intervals examined. There was no long term retention in any of the eyelid tissues examined.
The well described array of serious systemic side effects caused by the use of high systemic doses of doxorubicin as a chemotherapeutic agent made it critical to ascertain how long doxorubicin remained within the injected eyelids, and to determine to what extent and with what time course local injections of chemically intact doxorubicin might spread systemically. The short retention of the active or unmetabolized drug at the injection site is important, since more than one set of injections has been required for satisfactory amelioration of muscle spasms in blepharospasm and hemifacial spasm patients. The lack of detectable systemic spread of the drug distant from the local site of injection as well as the lack of long term retention of the locally injected doxorubicin lends support for the safety of doxorubicin administered in this manner to blepharospasm and hemifacial spasm patients.
一种针对良性特发性睑痉挛和半面痉挛的实验性治疗方法是将阿霉素直接注射到眼睑中以永久性地使肌肉失活。本研究检测了在眼睑局部注射低剂量阿霉素后其在局部和全身的扩散程度，并确定了注射后阿霉素在眼睑中保留的时间长度。
将2毫克阿霉素皮下注射到兔的下眼睑。在不同时间段后，取下眼睑并解剖成三个单独的标本，分别由皮肤、包括眼轮匝肌的皮下结缔组织或睑结膜组成。还收集了附近的组织，包括面部肌肉和眼外肌。收集尿液、血液、肾脏、脾脏、心脏和肝脏样本。所有组织均准备用于高效液相色谱法测定阿霉素浓度。
注射后的前4天，在所有三个眼睑标本中均检测到阿霉素，不过到第4天时阿霉素水平大幅降低。在第7天及之后，在治疗的眼睑组织中未检测到可检测水平的阿霉素。在所检查的任何注射后间隔时间，尿液或任何其他身体组织中均未检测到阿霉素水平。在所检查的任何眼睑组织中均未发现长期留存。
作为化疗药物使用高全身剂量阿霉素会引发一系列严重的全身副作用，因此确定阿霉素在注射的眼睑中留存多长时间，以及确定局部注射化学性质完整的阿霉素在多大程度上以及以何种时间进程可能会发生全身扩散至关重要。活性或未代谢药物在注射部位的短留存时间很重要，因为对于睑痉挛和半面痉挛患者，要使肌肉痉挛得到满意改善需要进行不止一组注射。未检测到药物在远离局部注射部位的全身扩散，以及局部注射的阿霉素没有长期留存，这为以这种方式给睑痉挛和半面痉挛患者使用阿霉素的安全性提供了支持。
