Physiological Pharmaceutics

258 Physiological PharmaceuticsFigure 11.8 Transcorneal penetration into the aqueous humour. The losses are significantand it usual for less than 5% of the instilled dose to penetrate into the intraocular tissuesfollowing a 25 ul drop.Protein bindingEstimates of the total protein content of tears range from 0.6 to 2% w/v, the major fractionsconsisting of albumin, globulin and lysozyme. Drugs bound to the protein in the tear fluidmay not permeate the cornea due to the additional bulk of the protein molecule; alsobinding of drugs to protein in conjunctival tissues competes for the drug available forcorneal absorption (Figure 11.8). Binding increases in certain disease states, particularlyinflammatory conditions, due to higher secretion of proteins in tissue exudate.If two drugs have to be applied to the same eye, an interval of five to ten minutesshould elapse between administration of each drug. If the second drug is applied too soonafter the first, it may displace the first drug, which will then be rapidly cleared, therebyreducing its effect.Pigmentation and drug effectsThere have been only a limited number of studies carried out in this area, but these suggestthat the intraocular distribution of drugs vary with levels of eye pigmentation. For example,a ten-fold increase in pilocarpine deposition in the iris-ciliary body of the pigmented rabbiteye is found when compared with albinos, although the pilocarpine concentration in theaqueous humor was indistinguishable between the two 4 . Pilocarpine is metabolised by tissue