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Intraocular Penetration of Topical Tissue Plasminogen Activator

Intraocular Penetration of Topical Tissue Plasminogen Activator Abstract • Fifty-eight eyes of 31 anesthetized rabbits received one drop of proparacaine hydrochloride, 0.05%, and two drops of tissue plasminogen activator (tPA) separated by 5 minutes. Four eyes of two additional rabbits had epithelial defects created before drug delivery. Tissue plasminogen activator in multiple doses was given to eight eyes of four other rabbits. We used this dosing regimen to investigate the effect of topical tPA on anterior chamber fibrin clots in three rabbits. A two-site enzyme-linked immunosorbent assay test was used to measure tPA levels in the aqueous samples, obtained by paracentesis in each eye. Of 53 eyes treated with the original dosing regimen, 21 (40%) had detectable tPA aqueous levels. Blood and aqueous from eyes of untreated control rabbits, contralateral control eyes of treated rabbits, and eyes with epithelial defects had nondetectable tPA. Multiple tPA drop dosing resulted in 75% of aqueous samples with detectable tPA and a higher average tPA concentration than the original dosing regimen. Eyes treated with tPA showed a significantly faster resolution of anterior chamber fibrin clots than did control eyes. References 1. Crabbe SJ, Cloninger CC. Tissue plasminogen activator: a new thrombolytic agent . Clin Pharm . 1987;6:373-386. 2. Lambrou FH, Snyder RW, Williams GA, Lewandowski M. Treatment of experimental intravitreal fibrin with tissue plasminogen activator . Am J Ophthalmol . 1987;104:619-623. 3. Snyder RW, Lambrou FH, Williams GA. Intraocular fibrinolysis with recombinant human tissue plasminogen activator . Arch Ophthalmol . 1987;105:1277-1280.Crossref 4. Johnson RN, Olsen K, Hernandez E. Tissue plasminogen activator treatment of postoperative intraocular fibrin . Ophthalmology . 1988;95:592-596.Crossref 5. Williams GA, Lambrou FH, Jaffe GA, et al. Treatment of postvitrectomy fibrin formation with intraocular tissue plasminogen activator . Arch Ophthalmol . 1988;106:1055-1058.Crossref 6. Dabbs CK, Aaberg TM, Aguilar HE, Sternberg P, Meredith TA, Ward AR. Complications of tissue plasminogen activator therapy after vitrectomy for diabetes . Am J Ophthalmol . 1990;110:354-360. 7. Mohler MA, Tate K, Bringman TS, et al. Circulatory metabolism of recombinant tissue-type plasminogen activator in monkeys and rabbits . Fibrinolysis . 1988;2:17-23.Crossref 8. Maurice DM, Mishima S. Ocular pharmacokinetics . In: Sears ML, ed. Pharmacology of the Eye . New York, NY: Springer-Verlag; 1984:19-102. 9. Cintron CR, Szamier RB, Hassinger LC, Kublin C. Scanning electron microscopy of rabbit corneal scars . Invest Ophthalmol Vis Sci . 1982;23:50-63. 10. Fujikawa LS, Foster CS, Harrist TJ, Lanigan JM, Colvin RB. Fibronectin in healing rabbit corneal wounds . Lab Invest . 1981;45:120-129. 11. Glasser DB, Gardner S, Ellis JG, Pettit TH. Loading doses and extended dosing intervals in topical gentamicin therapy . Am J Ophthalmol . 1985;99:329-332. 12. Ahmed I, Gokhale RD, Shah MV, Patton TF. Physiochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea . J Pharm Sci . 1987;76:583-586.Crossref 13. Ahmed I, Patton TF. Importance of the non-corneal absorption route in topical ophthalmic drug delivery . Invest Ophthalmol Vis Sci . 1985;26:584-587. 14. Leonard A, Hendrick A. Pupillary dilation with single eyedrop mydriatic combinations . Am J Ophthalmol . 1980;89:553-559. 15. Havener WH. Ocular Pharmacology . 5th ed. St Louis, Mo: CV Mosby Co; 1983:72-75. 16. Snyder RW, Williams GA, Lambrou FH. Clearance of intraocular fibrin using recombinant human tissue plasminogen activator . Invest Ophthalmol Vis Sci . 1987;28( (suppl) ):210. 17. Tripathi RC, Park JK, Tripathi BJ, Millard CB. Tissue plasminogen activator in human aqueous humor and its possible therapeutic significance . Am J Ophthalmol . 1988;106:719-722. 18. Yedavally S, Hartzer M, Williams GA. Plasminogen activator inhibitor (PAI) levels and activity in the human aqueous humor . Invest Ophthalmol Vis Sci . 1990;31( (suppl) ):508. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1991.01080050130043
Publisher site
See Article on Publisher Site

Abstract

Abstract • Fifty-eight eyes of 31 anesthetized rabbits received one drop of proparacaine hydrochloride, 0.05%, and two drops of tissue plasminogen activator (tPA) separated by 5 minutes. Four eyes of two additional rabbits had epithelial defects created before drug delivery. Tissue plasminogen activator in multiple doses was given to eight eyes of four other rabbits. We used this dosing regimen to investigate the effect of topical tPA on anterior chamber fibrin clots in three rabbits. A two-site enzyme-linked immunosorbent assay test was used to measure tPA levels in the aqueous samples, obtained by paracentesis in each eye. Of 53 eyes treated with the original dosing regimen, 21 (40%) had detectable tPA aqueous levels. Blood and aqueous from eyes of untreated control rabbits, contralateral control eyes of treated rabbits, and eyes with epithelial defects had nondetectable tPA. Multiple tPA drop dosing resulted in 75% of aqueous samples with detectable tPA and a higher average tPA concentration than the original dosing regimen. Eyes treated with tPA showed a significantly faster resolution of anterior chamber fibrin clots than did control eyes. References 1. Crabbe SJ, Cloninger CC. Tissue plasminogen activator: a new thrombolytic agent . Clin Pharm . 1987;6:373-386. 2. Lambrou FH, Snyder RW, Williams GA, Lewandowski M. Treatment of experimental intravitreal fibrin with tissue plasminogen activator . Am J Ophthalmol . 1987;104:619-623. 3. Snyder RW, Lambrou FH, Williams GA. Intraocular fibrinolysis with recombinant human tissue plasminogen activator . Arch Ophthalmol . 1987;105:1277-1280.Crossref 4. Johnson RN, Olsen K, Hernandez E. Tissue plasminogen activator treatment of postoperative intraocular fibrin . Ophthalmology . 1988;95:592-596.Crossref 5. Williams GA, Lambrou FH, Jaffe GA, et al. Treatment of postvitrectomy fibrin formation with intraocular tissue plasminogen activator . Arch Ophthalmol . 1988;106:1055-1058.Crossref 6. Dabbs CK, Aaberg TM, Aguilar HE, Sternberg P, Meredith TA, Ward AR. Complications of tissue plasminogen activator therapy after vitrectomy for diabetes . Am J Ophthalmol . 1990;110:354-360. 7. Mohler MA, Tate K, Bringman TS, et al. Circulatory metabolism of recombinant tissue-type plasminogen activator in monkeys and rabbits . Fibrinolysis . 1988;2:17-23.Crossref 8. Maurice DM, Mishima S. Ocular pharmacokinetics . In: Sears ML, ed. Pharmacology of the Eye . New York, NY: Springer-Verlag; 1984:19-102. 9. Cintron CR, Szamier RB, Hassinger LC, Kublin C. Scanning electron microscopy of rabbit corneal scars . Invest Ophthalmol Vis Sci . 1982;23:50-63. 10. Fujikawa LS, Foster CS, Harrist TJ, Lanigan JM, Colvin RB. Fibronectin in healing rabbit corneal wounds . Lab Invest . 1981;45:120-129. 11. Glasser DB, Gardner S, Ellis JG, Pettit TH. Loading doses and extended dosing intervals in topical gentamicin therapy . Am J Ophthalmol . 1985;99:329-332. 12. Ahmed I, Gokhale RD, Shah MV, Patton TF. Physiochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea . J Pharm Sci . 1987;76:583-586.Crossref 13. Ahmed I, Patton TF. Importance of the non-corneal absorption route in topical ophthalmic drug delivery . Invest Ophthalmol Vis Sci . 1985;26:584-587. 14. Leonard A, Hendrick A. Pupillary dilation with single eyedrop mydriatic combinations . Am J Ophthalmol . 1980;89:553-559. 15. Havener WH. Ocular Pharmacology . 5th ed. St Louis, Mo: CV Mosby Co; 1983:72-75. 16. Snyder RW, Williams GA, Lambrou FH. Clearance of intraocular fibrin using recombinant human tissue plasminogen activator . Invest Ophthalmol Vis Sci . 1987;28( (suppl) ):210. 17. Tripathi RC, Park JK, Tripathi BJ, Millard CB. Tissue plasminogen activator in human aqueous humor and its possible therapeutic significance . Am J Ophthalmol . 1988;106:719-722. 18. Yedavally S, Hartzer M, Williams GA. Plasminogen activator inhibitor (PAI) levels and activity in the human aqueous humor . Invest Ophthalmol Vis Sci . 1990;31( (suppl) ):508.

Journal

Archives of OphthalmologyAmerican Medical Association

Published: May 1, 1991

References

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