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

Purpose. An experimental treatment for benign essential blepharospasm and h emifacial spasm involves the direct injection of doxorubicin into the eyeli ds 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 t he eyelid after injection. Methods. Two mg doxorubicin was injected subcutaneously into the lower eyel ids of rabbits. After various time periods, the eyelids were removed and di ssected into three separate specimens consisting of skin, subcutaneous conn ective tissue including orbicularis oculi muscle, or palpebral conjunctiva. Nearby tissues were also collected, including facial muscles and extraocul ar muscles. Urine, blood, kidney, spleen, heart and liver samples were coll ected. All tissues were prepared for HPLC determination of doxorubicin conc entration. Results. Doxorubicin was detected in all three eyelid specimens for the fir st 4 days after injection, although by the fourth day the level of doxorubi cin was greatly reduced. On and after the seventh day, there was no detecta ble doxorubicin in the treated eyelid tissues. There were no detectable lev els 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 t he eyelid tissues examined. Conclusions. The well described array of serious systemic side effects caus ed by the use of high systemic doses of doxorubicin as a chemotherapeutic a gent made it critical to ascertain how long doxorubicin remained within the injected eyelids, and to determine to what extent and with what time cours e local injections of chemically intact doxorubicin might spread systemical ly. The short retention of the active or unmetabolized drug at the injectio n site is important, since more than one set of injections has been require d for satisfactory amelioration of muscle spasms in blepharospasm and hemif acial spasm patients. The lack of detectable systemic spread of the drug di stant from the local site of injection as well as the lack of long term ret ention of the locally injected doxorubicin lends support for the safety of doxorubicin administered in this manner to blepharospasm and hemifacial spa sm patients.