Ocular administration

This preservative has been used in a dry eye treatment and was shown in a clinical study to have the same biocompatibility as another marketed preparation [152]. Cetrimonium chloride (0.01%) produced the same corneal and conjunctival changes after one-month ocular administration in rats as the effective levels of other major preservatives [153],... 

Although the ocular absorption of peptide as well as nonpeptide drugs is poor [96,196-198], the ocular route is by far the least studied for the usefulness of penetration enhancers. This is in part due to the perceived sensitivity of ocular tissues to irritation and the fear of corneal and conjunctival damage caused by the enhancers. Whereas the rat nasal epithelium may tolerate up to 5% sodium glycocholate [199], ocular administration of sodium glycocholate at a concentration of 2% and beyond induces reddening of the eye and tear production in rabbits (Kompella and Lee, unpublished observation). 

C Losa, MJ Alonso, JL Vila, F Orallo, J Martinez, JA Saavedra, JC Pastor. (1992). Reduction of cardiovascular side effects associated with ocular administration of metipranolol by inclusion in polymeric nanocapsules. J Ocular Pharmacol 8 191-198. 

In a toxicity summary submitted by Eastman Kodak Company (1978), ocular administration of di-n-octylphthalate resulted in slight conjunctival irritation and no corneal damage. No further details were provided. 

P. Chetoni, P. Crotti, M. F. Saettone, Albuterol Prodrugs for Ocular Administration Synthesis and Evaluation of the Physicochemical and IOP-Depressant Properties of Three Albuterol Triesters , Int. J. Pharm. 1994, 105, 147-155. 

Pharmacokinetics After ocular administration of a 0.1% or 0.2% solution, plasma concentrations peaked within 0.5 to 2.5 hours and declined with a systemic half-life of approximately 2 hours. 

Aplastic anemia occurs in only about 1 in 24,000 to 40,000 cases of treatment. It is not a dose-related response and can occur either while the patient is taking chloramphenicol for days to months after completion of therapy. The aplastic or hypoplastic response involves all cellular elements of the marrow and is usually fatal. The mechanism is not known, but it occurs most frequently with oral or ocular administration. 

Studies in rabbits, monkeys and humans showed brinzolamide to be absorbed into the systemic circulation following topical ocular administration. Substantial levels (several micrograms per mL in whole blood) were achieved upon long term repeated dosing. 

Adverse effects associated with brinzolamide are similar to those of other carbonic anhydrase inhibitors. In clinical experience with topical ocular administration of brinzolamide, events including transient, momentary blurred vision, bitter, and sour or unusual taste were reported in approximately 5 % - 10% of patients. Ocular discomfort, discharge or other ocular signs, and headache were reported at an incidence of 1 -5% [15]. 

Pharmacokinetics Plasma concentrations peak within 0.5 to 2.5 hr after ocular administration. Distributed into aqueous humor. Metabolized in liver. Primarily excreted in urine. Half-life 3 hr. 

Pharmacokinetics The plasma concentration of bromfenac following ocular administration is unknown. 

Ahsan, F., et al. 2001. Enhanced bioavailability of calcitonin formulated with alkylglycosides following nasal and ocular administration in rats. Pharm Res 18 1742. 

A similar effect can be seen following ocular administration of micronized carbon suspensions in perfluorodecalin. This vehicle is a nonsolvent and because the powder is delivered dry, the particles attach during the first reflexive blink and disperse to the lash roots (Figure 23.2) [2]. 

Proving effective reversed targeting, which results from the soft nature of this steroid, systemic levels or effects cannot be detected even after chronic ocular administration [57], Plasma levels of loteprednol etabonate and its primary metabolite (PJ-91) were less than the 1 ng/L detection limit in 10 healthy volunteers who received the drug in both eyes eight times daily for 2 days and four times daily for a further 41 days [57], In addition to its already approved uses, loteprednol etabonate is also being developed for the treatment of colitis, atopic dermatitis, and asthma based on promising results from animal studies [47, 48],... 

J. Howes and G. D. Novack, Failure to detect systemic levels and effects of loteprednol etabonate and its metabolite, PJ-91, following chronic ocular administration, J. Ocul. Pharmacol. Ther 14 153 (1998). 

As mentioned above, the ability to adsorb to the cornea and an optimal drug release rate have been defined as the two liposomal attributes most responsible for increasing bioavailability after topical ocular administration. A number of factors, including drug encapsulation efficiency, liposome size and charge, distribution of the drug within liposomes, stability of liposomes in the conjunctival sac and ocular tissues, their retention in the conjunctival sac, and most importantly their affinity toward the corneal surface and the rate of release of the encapsulated drug, have... 

Although no adverse reactions have been reported with intranasal administration of propranolol, complications may occur, as ocular administration has produced some systemic side effects [118]. The influence of substrate lipophilicity on drug uptake by the nasal route was reported in humans. Alprenolol and metoprolol, 3 blockers with varying degrees of lipophilicity, were used. The findings from these studies demonstrate that the more hydrophilic drugs showed a lower bioavailability. Alprenolol showed rapid uptake into the systemic circulation by the nasal route and also a higher bioavailability [126,127]. 

Gasco and co-workers [221] investigated the potential application of o/w lecithin MEs for ocular administration of timolol, in which the drug was present as an ion pair with octanoate. The ocular bioavailability of the timolol ion pair incorporated into the ME was compared to that of an ion pair solution as well as a simple timolol solution. Areas under the curve for the ME and the ion pair solution respectively were 3.5 and 4.2 times higher than that of the simple timolol solution. A prolonged absorption was achieved using the ME with detectable amounts of the drug still present 120 min after instillation. 

Gasco, M. R., Gallarate, M.,Trotta, M., Bauchiero, L., Gremmo, E., and Chiappero, O. (1989), Microemulsions as topical delivery vehicles Ocular administration of timolol, J. Pharm. Biomed. Anal., 7(4), 433-439. 

Systemic Effects. Ocular administration of phenylephrine has been reported to induce acute hypertension (see Table 8-2). Sixty patients were studied after three applications of the 10% solution in each eye at 10-minute intervals.Thirty minutes after the last drop, systolic elevations of 10 to 40 mm Hg and diastolic elevations of 10 to 30 mm Hg occurred in all subjects. In each case pulse rate decreased 10 to 20 beats per minute. In contrast to these observations, however, other investigators reported a lack of systemic vasopressor response with the 10% concentration. 

Borromeo-McGrail V, Borduik J, Keitel H. Systemic hypertension following ocular administration of 10% phenylephrine in the neonate.J Pediatr 1973 51 1032-1036. 

Pharmacokinetic data indicate that ketorolac penetrates the cornea after topical ocular administration and reaches concentrations that reduce prostaglandin E levels in the aqueous humor. Plasma levels of ketorolac after topical ocular application are usually below detectable limits compared with oral administration. Ketorolac does not affect lOP, pupillary response, or visual acuity. 

Vogelson CT, Abelson MB, PasquineT, et al. PrecUnical and clinical antiallergic effect of olopatadine 0.2% solution 24 hours after topical ocular administration. Allergy Asthma Proc 2004 69-75. 

Disadvantage is that absorption can occur, especially when there is tissue destruction so that systemic effects result, e.g. adrenal steroids and neomycin to the skin, atropine to the eye. Ocular administration of a P-adrenoceptor blocker may cause systemic effects (any first-pass elimination is bypassed) and such eye drops are contraindicated for patients with asthma or chronic lung disease. There is extensive literature on this subject characterised by expressions of astonishment that serious effects, even death, can occur. 

Losa, C. Marchal-Heussler, L. Orallo, F. Vila Jato, J.L. Alonso, M.J. Design of new formulations for topical ocular administration polymeric nanocapsules containing metipranolol. Pharm. Res. 1993,10, 80-87. 

Beta-adrenoceptor antagonists are used as ocular tensionlowering drugs without notable effects on pupillary size or refraction. Their systemic effects are greater than one would expect, since there is no first-pass metabolism after ocular administration and the plasma concentration can therefore attain therapeutic concentrations (353). 

In 1993 the American National Register of Drug Induced Ocular Side Effects received reports of 23 patients with blood dyscrasias that could have been related to topical ocular administration of chloramphenicol (65). 

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