Doxorubicin does not spread systemically following a local injection into the eyelids of rabbits

Abstract

PURPOSE. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.