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Concentration Change of Fluorouracil in the External Segment of the Eye After Subconjunctival Injection FREE

Masaki Kondo, MD; Makoto Araie, MD
[+] Author Affiliations

Accepted for publication July 7, 1988.

Reprint requests to Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113, Japan (Dr Araie).


Arch Ophthalmol. 1988;106(12):1718-1721. doi:10.1001/archopht.1988.01060140890035
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• Five milligrams of fluorouracil was injected subconjunctivally in the rabbit eye, and its concentration changes in the cornea, aqueous humor, and conjunctiva and sclera (both at the injection site and 180° away from it) were determined by microbiological assay. The fluorouracil concentrations in the cornea and the aqueous humor averaged about 20 μg/g at one hour. The former decreased to 0.5 μg/g at 24 hours, while the latter was 0.03 μg/g at ten hours or later. At five hours, the fluorouracil concentrations in the conjunctiva and sclera at the injection site were similar to those 180° away from it, both averaging about 2 μg/g. They decreased to 0.3 through 0.9 μg/g at 24 hours. The fluorouracil concentrations in the cornea, conjunctiva, and sclera at 24 hours were still above the reported 50% inhibition levels for the cultured conjunctival fibroblast. These findings have potential clinical implications for the safe use of fluorouracil.

REFERENCES

Heuer DK, Parrish RK II, Gressel MG, et al:  5-Fluorouracil and glaucoma filtering surgery: III. Intermediate follow-up of a pilot study . Ophthalmology 1986;;93:1537-1546.
Weinreb RN:  Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects . Ophthalmology 1987;;94:564-570.
Rockwood EJ, Parrish RK II, Heuer DK, et al:  Glaucoma filtering surgery with 5-fluorouracil . Ophthalmology 1987;;94:1071-1078.
Ruderman JM, Welch DB, Smith MF, et al:  A randomized study of 5-fluorouracil and filtration surgery . Am J Ophthalmol 1987;;104:218-224.
Fantes EF, Parrish RK II, Heuer DK, et al:  Subconjunctival 5-fluorouracil mechanisms of ocular penetration . Ophthalmic Surg 1987;;18:375-378.
Rootman J, Tisdall J, Gudauskas G, et al:  Intraocular penetration of subconjunctivally administered 14C-fluorouracil in rabbits . Arch Ophthalmol 1979;;97:2375-2378.
Myers CE:  The pharmacology of the fluoropyrimidines . Pharmacol Rev 1981;;33:1-15.
Stern WH, Guerin CJ, Erickson PA, et al:  Ocular toxicity of fluorouracil after vitrectomy . Am J Ophthalmol 1983;;96:43-51.
Knapp A, Heuer DK, Stern GA, et al:  Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil . Am J Ophthalmol 1987;;103:183-187.
Grant WM: Toxicology of the Eye , ed 2. Springfield, Ill, Charles C Thomas Publisher, 1974;, p 718.
Kunitomo N, Mori S:  Studies on the pterygium: IV. A treatment of the pterygium by mitomycin C instillation . Acta Ophthalmol Soc Jpn 1963;;67:601-607.
Yamanouchi U, Mishima K:  Eye lesions due to mitomycin C instillation after pterygium operation . Folia Ophthalmol Jpn 1967;;18:854-861.
Addicks EM, Quigley HA, Green WR, et al:  Histologic characteristics of filtering blebs in glaucomatous eyes . Arch Ophthalmol 1983;;101:795-798.
Skuta GL, Parrish RK II:  Wound healing in glaucoma filtering surgery . Surv Ophthalmol 1987;;32:149-170.
Clarkson B, O'Conner A, Winston L, et al:  The physiologic deposition of 5-fluorouracil and 5-fluoro-2'-deoxyuridine in man . Clin Pharmacol Ther 1964;;5:581-610.
Fujita H, Ogawa K, Nakazawa H, et al:  Pharmacokinetics of 5'-deoxy-fluorouridine (5'-DFUR) by oral administration . J Jpn Soc Cancer Ther 1983;;18:916-926.
Felchlin M:  Versuche zur Ermittlung des spezifischen Gewichts der verschiedenen Augenmedien mittlels einer neuen Methode . Graefes Arch Clin Exp Ophthalmol 1926;;117:325-342.
Blumenkranz MS, Claflin A, Hajek AS:  Selection of therapeutic agents for intraocular proliferative disease . Arch Ophthalmol 1984;;102:598-604.
Mallick KS, Hajek AS, Parrish RK II:  Fluorouracil (5-FU) and cytarabine (Ara-C) inhibition of corneal epithelial cell and conjunctival fibroblast proliferation . Arch Ophthalmol 1985;;103:1398-1402.
Blumenkranz MS, Hartzer MK, Hajek AS:  Selection of therapeutic agents for intraocular proliferative disease: II. Differing antiproliferative activity of the fluoropyrimidines . Arch Ophthalmol 1987;;105:396-399.
Havener WH:  Pharmacokinetics: Routes of administration , in Ocular Pharmacology , ed 5. St Louis, CV Mosby Co; 1983;, pp 18-43.
Tsuchiya M, Hayasaka S, Mizuno K:  Affinity of ocular acid-insoluble melanin for drugs in vivo . Invest Ophthalmol Vis Sci 1987;;28:822-825.
Lee DA, Flores RA, Anderson PJ, et al:  Glaucoma filtration surgery in rabbits using bioerodible polymers and 5-fluorouracil . Ophthalmology 1987;;94:1523-1530.
Smith TJ, Maurin MB, Milosovich SM, et al:  A membrane based sustained release ocular delivery system for 5-fluorouracil , abstracted. Invest Ophthalmol Vis Sci 1987;;28( (suppl) ):271.
Heath TD, Lopez NG, Lewis GP, et al:  Antiproliferative and anticontractile effects of liposome encapsulated fluoroorotate . Invest Ophthalmol Vis Sci 1987;;28:1365-1372.
Goodman DF, Alvarado JA, Stern W, et al:  Liposomal incorporated 5-fluoroorotate inhibition of wound healing following posterior lip sclerotomy in the primate , abstracted. Invest Ophthalmol Vis Sci 1987;;28( (suppl) ):271.

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Heuer DK, Parrish RK II, Gressel MG, et al:  5-Fluorouracil and glaucoma filtering surgery: III. Intermediate follow-up of a pilot study . Ophthalmology 1986;;93:1537-1546.
Weinreb RN:  Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects . Ophthalmology 1987;;94:564-570.
Rockwood EJ, Parrish RK II, Heuer DK, et al:  Glaucoma filtering surgery with 5-fluorouracil . Ophthalmology 1987;;94:1071-1078.
Ruderman JM, Welch DB, Smith MF, et al:  A randomized study of 5-fluorouracil and filtration surgery . Am J Ophthalmol 1987;;104:218-224.
Fantes EF, Parrish RK II, Heuer DK, et al:  Subconjunctival 5-fluorouracil mechanisms of ocular penetration . Ophthalmic Surg 1987;;18:375-378.
Rootman J, Tisdall J, Gudauskas G, et al:  Intraocular penetration of subconjunctivally administered 14C-fluorouracil in rabbits . Arch Ophthalmol 1979;;97:2375-2378.
Myers CE:  The pharmacology of the fluoropyrimidines . Pharmacol Rev 1981;;33:1-15.
Stern WH, Guerin CJ, Erickson PA, et al:  Ocular toxicity of fluorouracil after vitrectomy . Am J Ophthalmol 1983;;96:43-51.
Knapp A, Heuer DK, Stern GA, et al:  Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil . Am J Ophthalmol 1987;;103:183-187.
Grant WM: Toxicology of the Eye , ed 2. Springfield, Ill, Charles C Thomas Publisher, 1974;, p 718.
Kunitomo N, Mori S:  Studies on the pterygium: IV. A treatment of the pterygium by mitomycin C instillation . Acta Ophthalmol Soc Jpn 1963;;67:601-607.
Yamanouchi U, Mishima K:  Eye lesions due to mitomycin C instillation after pterygium operation . Folia Ophthalmol Jpn 1967;;18:854-861.
Addicks EM, Quigley HA, Green WR, et al:  Histologic characteristics of filtering blebs in glaucomatous eyes . Arch Ophthalmol 1983;;101:795-798.
Skuta GL, Parrish RK II:  Wound healing in glaucoma filtering surgery . Surv Ophthalmol 1987;;32:149-170.
Clarkson B, O'Conner A, Winston L, et al:  The physiologic deposition of 5-fluorouracil and 5-fluoro-2'-deoxyuridine in man . Clin Pharmacol Ther 1964;;5:581-610.
Fujita H, Ogawa K, Nakazawa H, et al:  Pharmacokinetics of 5'-deoxy-fluorouridine (5'-DFUR) by oral administration . J Jpn Soc Cancer Ther 1983;;18:916-926.
Felchlin M:  Versuche zur Ermittlung des spezifischen Gewichts der verschiedenen Augenmedien mittlels einer neuen Methode . Graefes Arch Clin Exp Ophthalmol 1926;;117:325-342.
Blumenkranz MS, Claflin A, Hajek AS:  Selection of therapeutic agents for intraocular proliferative disease . Arch Ophthalmol 1984;;102:598-604.
Mallick KS, Hajek AS, Parrish RK II:  Fluorouracil (5-FU) and cytarabine (Ara-C) inhibition of corneal epithelial cell and conjunctival fibroblast proliferation . Arch Ophthalmol 1985;;103:1398-1402.
Blumenkranz MS, Hartzer MK, Hajek AS:  Selection of therapeutic agents for intraocular proliferative disease: II. Differing antiproliferative activity of the fluoropyrimidines . Arch Ophthalmol 1987;;105:396-399.
Havener WH:  Pharmacokinetics: Routes of administration , in Ocular Pharmacology , ed 5. St Louis, CV Mosby Co; 1983;, pp 18-43.
Tsuchiya M, Hayasaka S, Mizuno K:  Affinity of ocular acid-insoluble melanin for drugs in vivo . Invest Ophthalmol Vis Sci 1987;;28:822-825.
Lee DA, Flores RA, Anderson PJ, et al:  Glaucoma filtration surgery in rabbits using bioerodible polymers and 5-fluorouracil . Ophthalmology 1987;;94:1523-1530.
Smith TJ, Maurin MB, Milosovich SM, et al:  A membrane based sustained release ocular delivery system for 5-fluorouracil , abstracted. Invest Ophthalmol Vis Sci 1987;;28( (suppl) ):271.
Heath TD, Lopez NG, Lewis GP, et al:  Antiproliferative and anticontractile effects of liposome encapsulated fluoroorotate . Invest Ophthalmol Vis Sci 1987;;28:1365-1372.
Goodman DF, Alvarado JA, Stern W, et al:  Liposomal incorporated 5-fluoroorotate inhibition of wound healing following posterior lip sclerotomy in the primate , abstracted. Invest Ophthalmol Vis Sci 1987;;28( (suppl) ):271.

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