PHARMACOKINETICS OF ETOPOSIDE DELIVERY BY A BIOERODIBLE DRUG CARRIER IMPLANTED AT GLAUCOMA SURGERY

Purpose: Pharmacological modulation of wound healing after glaucoma fi ltration surgery is of great clinical interest, but there are only lim ited data available on drug pharmacokinetics following glaucoma filtra tion surgery. Therefore we have studied the in vivo release and tissue distribution of etoposide (VP-16) delivered subconjunctivally by a bi oerodible drug-carrier during filtration surgery in rabbits. Methods: Disks composed of the polyanhydride 1,3-bis(p-carboxyphenoxy) propane and sebacic acid (PCPP:SA) in a weight ratio of 25:75 and containing 1 mg of H-3-etoposide were placed subconjunctivally during posterior li p sclerectomy in one eye of albino rabbits. Animals were euthanized at various times after surgery and etoposide concentrations in fluids an d tissues were determined using liquid scintillation counting. Results : Release of etoposide from the implant was nearly linear over time, a t 30 ug/day, except for a burst between days 6 and 7. By the twelfth p ostoperative day, 92% of the etoposide had been released. Steady state levels averaged 89 ng/mg in the conjunctiva and sclera, 195 ng/ml in the vitreous, and 29 ng/ml in serum. Drug levels in the aqueous humor, other ocular tissues, and in the contralateral eye were negligible. C onclusions; The concentration of etoposide delivered by a polyanhydrid e controlled release device on the ocular surface is sufficient to red uce fibroblast proliferation for at least 12 days after filtration sur gery.