Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of Various Topical Ophthalmic Delivery Systems

  • Review Article
  • Drug Delivery Systems
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

The eye provides an interesting study in contrasts: it is a delicate structure with a transparent anterior wall as thin as 0.5mm; yet this structure in combination with the ocular adnexa provides a resilient physicochemical barrier. The lids, tears and lacrimal apparatus work in concert to continuously protect the cornea and conjunctiva with a stable tear film, which also serves as the primary refracting surface. This elaborate defence system simultaneously prevents ready intraocular access of pharmaceutical agents. Additionally, the trilaminate structure of the cornea has variable permeability to chemical agents, thereby further limiting the passage of highly hydrophobic and hydrophilic moieties.

Presenting topical pharmaceutical agents to the eye via different delivery systems allows clinicians to directly affect the profile of drug bioavailability and, ultimately, bioactivity. While achieving optimum bioavailability is therapeutically important, one must simultaneously limit the occurrence of drug-induced adverse effects, both systemic and local. Utilising the different pharmacokinetic properties of drug delivery systems permits clinicians to maximise their therapeutic plans for addressing specific clinical situations while minimising the potential for adverse drug effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mishima S, Gassett A, Klyce SD, et al. Determination of tear volume and flow. Invest Ophthalmol 1966; 5: 264–576

    PubMed  CAS  Google Scholar 

  2. Lesk MR, Ammann H, Marcil G, et al. The penetration of oral ciprofloxacin into the aqueous humor, vitreous and subretinal fluid of humans. Am J Ophthalmol 1993; 115: 623–8

    PubMed  CAS  Google Scholar 

  3. Shell JW. Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol 1982; 26: 207–18

    Article  PubMed  CAS  Google Scholar 

  4. Lee VHL, Urrea PT, Smith RE, et al. Ocular bioavailability from topically applied lysozomes. Surv Ophthalmol 1985; 29:335–48

    Article  PubMed  CAS  Google Scholar 

  5. Goldman JW, Benedik BH, Dohlman CH, et al. Structural alterations affecting transparency in swollen human corneas. Invest Ophthalmol 1968; 7: 501–19

    PubMed  CAS  Google Scholar 

  6. Benet LZ, Mitchell JR, Sheiner LB. General principles. In: Gilman AG, Rall TW, Nies As, et al, editors. The pharmacological basis of therapeutics. 6th ed. New York: Pergamon Press, 1990; 3–32

    Google Scholar 

  7. Zimmerman TJ, Kooner KS, Kandarakis AS, et al. Improving the therapeutic index of topically applied ocular drugs. Arch Ophthalmol 1984; 102:551–3

    Article  PubMed  CAS  Google Scholar 

  8. Wei C, Anderson JA, Leopold I. Ocular absorption and metabolism of topically applied epinephrine and a dipivalyl ester of epinephrine. Invest Ophthalmol Vis Sci 1978; 17: 315–21

    PubMed  CAS  Google Scholar 

  9. Krieglstein GK, Leydhecker W. The dose response relationships of dipivalyl epinephrine in open angle glaucoma. Al-brecht von Graefes Arch Ophthalmol 1978; 205: 141–6

    CAS  Google Scholar 

  10. Kass MA, Mandell AI, Goldberg I, et al. Dipivefrin and epinephrine treatment of elevated intraocular pressure. Arch Ophthalmol 1979; 97: 1865–6

    Article  PubMed  CAS  Google Scholar 

  11. Kohn AM, Moss AP, Hargett NA, et. Clinical comparison of dipivalyl epinephrine and epinephrine in treatment of glaucoma. Am J Ophthalmol 1979; 87: 196–201

    PubMed  CAS  Google Scholar 

  12. Schoenwald RD, Stewart D. Effect of particle size on ophthalmic bioavailability of dexamethasone suspensions in rabbits. J Pharm Sci 1980; 69(4): 391–4

    Article  PubMed  CAS  Google Scholar 

  13. Leibowitz HM, Kupferman A. Bioavailability and therapeutic effectiveness of topically administered corticosteroids. Trans Am Acad Ophthalmol Otol 1975; 79: 78–88

    Google Scholar 

  14. Polansky JR. Side effects of topical ophthalmic therapy with antiinflammatory steroids. Curr Opin Ophthalmol 1992; 3: 259–72

    Article  Google Scholar 

  15. Gardner S. Comparison of topical ophthalmic corticosteroid drops. Ocul Ther Manage 1992; 3(2); 1–14

    Google Scholar 

  16. Apt L, Hendrick A, Silverman LM. Patient compliance with use of topical ophthalmic corticosteroid suspensions. Am J Ophthalmol 1979; 87: 210–4

    PubMed  CAS  Google Scholar 

  17. Haas J, Merrill DL. The effects of methylcellulose on responses to solutions of pilocarpine. An J Ophthalmol 1962; 54: 21–4

    CAS  Google Scholar 

  18. Mueller WH, Deardorff DL. Ophthalmic vehicles: the effect of methylcellulose on the penetration of homatropine hydrobromide through the cornea. J Am Pharmacol Assoc 1956; 45:334–41

    Article  CAS  Google Scholar 

  19. Hardberger R, Hanna C, Boyd CM. Effects of drug vehicles on ocular contact time. Arch Ophthalmol 1975; 93: 42–5

    Article  PubMed  CAS  Google Scholar 

  20. Cox WV, Kupferman A, Leibowitz HM. Topically applied corticosteroids in corneal disease, II: the role of drug vehicle in the stromal absorption of dexamethasone. Arch Ophthalmol 1972; 88: 549–53

    Article  PubMed  CAS  Google Scholar 

  21. Grass GM, Robinson JR. Relationship of chemical structure to corneal penetration and influence of low-viscosity solution on ocular bioavailability. J Pharm Sci 1984; 73(8): 1021–7

    Article  PubMed  CAS  Google Scholar 

  22. Leibowitz HM. Hydrophilic contact lenses in corneal disease, IV: penetrating corneal wounds. Arch Ophthalmol 1972; 88: 602–8

    Article  PubMed  CAS  Google Scholar 

  23. Leibowitz HM, Rosenthal P. Hydrophilic contact lenses in corneal disease. Arch Ophthalmol 1971; 85: 283–5

    Article  PubMed  CAS  Google Scholar 

  24. Cavanaugh HD, Colley A, Pihlaja DJ. Persistent corneal epithelial defects. Int Ophthalmol Clin 1979; 19(2): 197–206

    Google Scholar 

  25. Podos SM, Becker B, Assoff C, et al. Pilocarpine therapy with soft contact lenses. Am J Ophthalmol 1972; 73: 336–41

    PubMed  CAS  Google Scholar 

  26. Shell JW, Barker R. Diffusional systems for controlled release of drugs to the eye. Ann Ophthalmol 1974; 6(10): 1037–45

    PubMed  CAS  Google Scholar 

  27. Musco PS, Aquavella JV. Therapeutic contact lenses. In: Dabezies OH, editor. Contact lenses. The CLAO guide to basic science and clinical practice. 8th ed. Boston: Little, Brown & Co., 1991; Chap. 46, 1–16

    Google Scholar 

  28. Praus P, Krejci L. Tetracycline: release from hydrophilic gel contact lens and intraocular penetration. Ophthalmol Res 1977; 9: 13–8

    Article  Google Scholar 

  29. Barza M, Baum J. Ocular pharmacology of antibiotics. In: Duane TD, Jaeger EA, editors. In: Biomedical foundations of ophthalmology. Philadelphia: JB Lippincott Co, 1993: 1–14

    Google Scholar 

  30. Maguen E, Nesburn AB. Complications of therapeutic lenses. In: Dabezies OH, editor. Contact lenses. The CLAO guide to basic science and clinical practice. 8th ed. Boston: Little, Brown & Co., 1991; Chap. 48, 1–8

    Google Scholar 

  31. Aquavella JV. Therapeutic use of hydrophilic contact lenses in corneal disease. In: Leibowitz HM, editor. Corneal disorders. Clinical diagnosis and management. Philadelphia: WB Saunders Co., 1984; Chap. 30, 652–77

    Google Scholar 

  32. Bloomfield SE, Miyata T, Dunn MC, et al. Soluble gentamicin ophthalmic inserts as a drug delivery system. Arch Ophthalmol 1978; 96: 885–7

    Article  PubMed  CAS  Google Scholar 

  33. Hobden JA, Reidy JJ, O’Callaghan RJ, et al. Treatment of experimental pseudomonas keratitis using collagen shields containing tobramycin. Arch Ophthal 1988; 106: 1605–7

    Article  PubMed  CAS  Google Scholar 

  34. Phinney RB, Schwartz SD, Lee DA, et al. Collagen-shield delivery of gentamicin and vancomycin. Arch Ophthalmol 1988; 106: 1599–604

    Article  PubMed  CAS  Google Scholar 

  35. Hwang DG, Stein WH, Hwang PH, et al. Collagen shield enhancement of topical dexamethasone penetration. Arch Ophthalmol 1989; 107:1375–80

    Article  PubMed  CAS  Google Scholar 

  36. Bawa R. Ocular inserts. In: Mitra AK, editor. Ophthalmic drug delivery systems. New York: Marcel Dekker, Inc, 1993:223–60

    Google Scholar 

  37. Pavan-Langston D, Langston RHS, Geary PA. Idoxuridine ocular insert therapy. Arch Ophthalmol 1975; 93: 1349–51

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cornea and External Diseases Service, Boston University School of Medicine, and Boston City Hospital, Boston, Massachusetts, USA

    John P. Frangie (Director)

Authors
  1. John P. Frangie
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frangie, J.P. Clinical Pharmacokinetics of Various Topical Ophthalmic Delivery Systems. Clin. Pharmacokinet. 29, 130–138 (1995). https://doi.org/10.2165/00003088-199529020-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199529020-00006

Keywords

Search

Navigation