Ophthalmic Drug Delivery Systems - part 2 pdf

... Ocularpharmacokineticsincludesthefeaturesofabsorption,distribu-tion,andexcretionfoundwithsystemicadministrationbutappliedtotheeye.However,owingtotheuniqueanatomyandphysiologyoftheeyeandsurroundingtissue,ocularpharmacokineticsisconsiderablymoredifficulttodescribeandpredictthanitssystemiccounterpart.Thetaskisfurthercomplicatedbythevariousformulations,routes,anddosingregimenstypi-callyencounteredinophthalmology.Pharmacodynamicsisthemeasurementofpharmacologicalresponserelativetodoseorconcentration.Thepharmacologicalresponseinducedbyadrugcanvarygreatlyfromindividualtoindividualduetodifferencesinfactorssuchaseyepigmentation,thepathologicalstateoftheeye,tearing,orblinkrate.Theapplicationofpharmacologicalendpointsisparticularlyusefulinthestudyofdrugsinthehumaneye,wheretheabilitytodeterminetheocularpharmacokineticsbasedonoculartissueconcentrationsisseverelylimited.Thischapterdiscussestheocularpharmacokineticsassociatedwithtopicalocular,intravitreal,periocular,andsystemicadministration.Inaddi-tion,thepharmacodynamicsrelatedtoophthalmicdrugsandtheroleofoculardrugmetabolismarereviewed.II.OCULARPHARMACOKINETICSApplicationofclassicalpharmacokineticstoophthalmicdrugsisprob-lematicbecauseofthecomplexitiesassociatedwitheyeanatomyandphy-siology.Asaresult,mostoftheliteratureislimitedtomeasuringconcentrationsinoculartissuesovertimefollowingsingleormultipleadministration.Thisapproach,whileinformative,doesnoteasilyyieldquantitativepredictionsforchangesinformulationordosageregimen.Compoundingtheproblemisthefactthatmoststudieshavebeenconductedinrabbiteyes,whichdiffersignificantlyfromhumaneyesinanatomyandphysiology(seeTable1).themostobviousdifferencesareinblink ... Ocular drug delivery. Pharmacokinetic considera-tions. Clin. Pharmacokinet., 18 :25 5.6. Lang, J. C., and Stiemke, M. M. Biological barriers to ocular delivery. In:Ocular Therapeutics and Drug Delivery ... of -blocking agents III: In vitro– in vivo correlations. J. Pharm.Sci., 72: 127 9.46. Tang-Liu, D. D. S., Liu, S. S., and Weinkam, R. J. (1984). Ocular and sys-temic bioavailability of ophthalmic...

... intraocular sur-gery. Ophthalmology 98 :22 7 22 8, 1991. 24 . Peyman, G. A., and Schulman, J. A. Intravitreal drug therapy. In: IntravitrealSurgery. Norwalk: Appleton-Century-Crofts, pp. 407–455. 25 . Speaker, ... Sci. 26 :698–710, 1985.17. Lund-Andersen, H., Krogsaa, B., and Larsen, J. Calculation of the perme-ability of the blood-retinal barrier to fluorescein. Graef. Arch. Clin. Exp.Ophth. 22 2:173–176, ... 90: 121 – 125 ,1983. 27 . Goldberg, M. F. Diseases affecting the inner blood-retinal barrier. In: TheBlood-Retinal Barriers, Cunha-Vaz, J. G., eds. New York: Plenum Press, 1979,pp. 309–363. 28 ....

... of a series of 50-ester prodrugs of 5-iodo -2 0-deoxyuridine. Pharm.Res. 5:734–737, 1988.10 Macha et al.Copyright © 20 03 Marcel Dekker, Inc. Ophthalmic Drug Delivery Systems Second Edition, ... forms (21 ,22 ).Instilled dose leaves the precorneal area within 5 minutes of instillation inhumans (21 ,23 ). The natural tendency of the cul-de-sac is to reduce its fluidvolume to 7–10 mL (24 26 ). ... 181StuartFriedrich,BradleySaville,andYu-LingCheng7. Anterior Segment Microdialysis 22 3KayD.Rittenhouse8. Posterior Segment Microdialysis 25 1SreerajMachaandAshimK.MitraIII.DrugDeliverySystemsA:ConventionalSystems9....

... at 4, 12, and 24 hours after injection,increased as the drug diffusivity was reduced. Furthermore, the rate of drug elimination, which is inversely related to the drug s elimination half-life, ... Ophthalmol. 22 8:461–466, 1990.36. Tsukahara, Y., and Maurice, D. M., Local pressure effects on vitreouskinetics. Exp. Eye Res. 60:563–574, 1995. Drug Distribution in Vitreous Humor 22 1Copyright © 20 03 ... sensitivityof drug distribution and elimination using the model. Therefore, the diffu-sivities used in the model simulations are 2: 4 Â 10À5cm 2 /s ( 125 Da), 5:6 Â10À6cm 2 /s (354 Da), and...

... applied ophthalmic drugs,Surv. Ophthalmol., 26 :20 7 21 8.88. Mikkelson, T. J. (1984). Review: Ophthalmic drug delivery, Pharm. Tech.,8:90–98.89. Lee, V. H. L. (1985). Review: Topical ocular drug delivery recent ... researchers. Br. J. Ophthalmol., 20 :21 3 22 9. 22 . Erlanger, G. (1939). Iontophoretic medication in ophthalmology. Theoreticand practical aspects. Arch. Phys. Ther., 20 :16 24 . 23 . Erlanger, G. (1954). ... Res., 15:18 82 1887. 128 . Peyman, G. A., and Ganiban, G. J. (1995). Delivery systems for intraocularroutes, Adv. Drug Delivery Rev., 16:107– 123 . 129 . Geroski, D. H., and Edelhauser, H. F. (20 00)....

... rhodop-sin mutation were protected from apoptosis by recombinant adeno-associated virus-mediated production of fibroblast growth factors fgf -2 , fgf-5, and fgf-18 (30,31), while lens epithelium-derived ... Atursson, P. (1990). Absorption of vasopressin analogue, 1- desamino-8-D-arginine-vasopressin (dDAVP), in human intestinal epithelialcell line, CaCO -2 , Int. J. Pharm., 64:181.43. Amidon, G. L., Sinko, ... and uterinearteries and their inhibition by deamino-ethyl-lysine-vasopressin and dea-mino-ethyl-oxytocin, Br. J. Obstet. Gynaecol., 90:7 32. 5. Vilhardt, H., and Bie, P. (1983). Antidiuretic...

... Science, 28 7(5460) :20 32 20 36.53. Ahmed, I., Tang, L., and Pham, H. (20 00). Identification of neural progeni-tors in the adult mammalian eye. Biochem. Biophys. Res. Commun., 27 0 (2) :517– 521 .54. ... scavenger, N-tert-butyl- ( 2- sulfoph-enyl)-nitrone (S-PBN), resulted in the survival of 63% axotomized RGCs,indicating the clinical usefulness of the approach for treating RGCs follow-ing optic ... Invest.Ophthalmol. Vis. Sci., 40 (2) :27 3 27 9.113. Bennett, J., Zehng, Y., Bajwa, R., Klatt, L., Li, Y., and Maguire, A. M.(1998). Adenovirus-mediated delivery of rhodopsin-promoted bc 1 -2 resultsin a delay...