title: Pharmacokinetics of etoposide delivery by a bioerodible drug carrier implanted at glaucoma surgery.
abstract: OBJECTIVE
  Pharmacological modulation of wound healing after glaucoma filtration surgery is of great clinical interest, but there are only limited data available on drug pharmacokinetics following glaucoma filtration surgery. Therefore we have studied the in vivo release and tissue distribution of etoposide (VP-16) delivered subconjunctivally by a bioerodible 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 3H-etoposide were placed subconjunctivally during posterior lip sclerectomy in one eye of albino rabbits. Animals were euthanized at various times after surgery and etoposide concentrations in fluids and tissues were determined using liquid scintillation counting.
  
  
  RESULTS
  Release of etoposide from the implant was nearly linear over time, at 30 ug/day, except for a burst between days 6 and 7. By the twelfth postoperative 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.
  
  
  CONCLUSIONS
  The concentration of etoposide delivered by a polyanhydride controlled release device on the ocular surface is sufficient to reduce fibroblast proliferation for at least 12 days after filtration surgery.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: P
authors.initials: P
authors.lastname: Uppal
authors.forename: H D
authors.initials: HD
authors.lastname: Jampel
authors.forename: H A
authors.initials: HA
authors.lastname: Quigley
authors.forename: K W
authors.initials: KW
authors.lastname: Leong
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D004337:Drug Carriers; D004343:Drug Implants; D005047:Etoposide / Q000493:pharmacokinetics*; D005123:Eye / Q000378:metabolism*; D005901:Glaucoma / Q000473:pathology / Q000601:surgery*; D008297:Male; D011817:Rabbits; D014130:Trabeculectomy; D014945:Wound Healing / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D005047:Etoposide