摘要:

ABSTRACTThe object of this study was to test whether flat, circular ophthalmic inserts releasing drug only from one side, would show improved activity parameters and reduced systemic absorption. To this purpose, uncoated and one-side coated hydroxypropylcellulose inserts containing timolol were prepared and evaluated. An acrylic copolymer (Eudragit® RS) was used as coating material. Timolol release from inserts was studied both in vitro and in vivo. Timolol release in vitro from the coated inserts was much slower than from the uncoated ones, due to the smaller releasing surface area. Compared with timolol eyedrops (0.5%, 50 μl), administration of 250 μg of timolol in uncoated or coated inserts produced a significantly greater hypotensive effect at 6 and 8 hr post instillation in rabbits with artificially increased intraocular pressure. The coated inserts containing 62.5 μg of timolol antagonised isoproterenol-induced ocular hypotension significantly more than timolol eyedrops (0.5%, 12.5 μ) and uncoated inserts containing 62.5 μg of timolol. Both uncoated and coated inserts provided a significant sustaining of timolol release in tear fluid and decreased systemic peak concentrations of timolol with respect to the eyedrop control. However, one-side coated inserts failed to show significant improvements with respect to the uncoated sa

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.1

年代:1993

数据来源: MAL

摘要:

ABSTRACTAntiglaucoma drugs were studied systematically on the ocular blood flow in ocular hypertensive rabbits. As expected, pilocarpine, clonidine and acetazolamide were all found to increase the ocular blood flow in the retina and choroid. However, their use in the clinics was much less than the β-blockers, such as L-timolol, levobunolol, betaxolol and metipranolol. It was surprising to find that all non-specific and β1-specific adrenergic blockers decreased the ocular blood flow in ocular hypertensive rabbits. If this finding holds true in human patients, the use of β-blockers for glaucoma treatment should be reconsidered. Dopamine antagonists, such as droperidol, metoclopramide and loxapine, were found to increase the ocular blood flow. Therefore, they might be able to replace β-blockers for glaucoma treatm

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.13

年代:1993

数据来源: MAL

摘要:

ABSTRACTAb internopulsed dye laser sclerostomy uses a gonioscopic approach to form a limbal fistula for the treatment of glaucoma. This procedure requires a full thickness penetration of stain in sclera for adequate absorption of the visible light energy. Iontophoresis is a technique using an electrical current to noninvasively deliver Reactive Black 5 (RB5) stain into sclera. This project determined the stability of RB5 stain as well as the optimal parameters for iontophoresis (probe tip surface area, current, and duration) in a rabbit model. RB5 stain was stable over time (72 hr) as well as after exposure to extreme heat (120°C), scleral constituents (namely collagen), high concentrations of oxidants (1.5% H2O2), and laser light energy. Ideal parameters for iontophoresis included a probe tip surface area between 0.1 and 0.7 mm2, a current of 0.5 mA, and a duration of 5 min. The maximum concentration of RB5 stain achieved in sclera was 0.15%. The threshold of ablation for RB5 using an energy of 250 mJ was 0.001%. Iontophoresis can effectively deliver RB5 stain into sclera and may be a viable adjunct toab internopulsed dye laser sclerostomy procedures in the eye

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.25

年代:1993

数据来源: MAL

摘要:

ABSTRACTTo locate suitable candidates to study the intraocular pressure (IOP) effects of new ocular steroids, healthy volunteers must be challenged with topically applied steroids to verify that such individuals are indeed high "steroid responders"; that is, they respond with IOP elevations of at least 5 mmHg during a 4- to 6-week challenge with the topically applied steroid. We used first-degree offspring of individuals with primary open-angle glaucoma to develop a model to identify high steroid responders to topical ophthalmic prednisolone. We conducted a prospective, randomized, open-label, placebo-controlled study of prednisolone phosphate 1.0% in which 13 subjects received either topical prednisolone phosphate 4 times daily to the right eye and placebo to the left eye, or vice versa. Baseline evaluations occurred on study Day 0, and follow-up examinations were on Days 7, 14, 21, 28, 35, and 42. The medications were administered continuously for 6 weeks or until the IOP rose ≥ 10 mmHg. After the effect of diurnal variation in IOP was taken into account, 4 of the 13 subjects (31%) had a maximum elevation in IOP of 4 mmHg or less, 7 subjects (54%) showed maximum elevations in IOP of 5 to 9 mmHg, and 2 subjects (15%) had a maximum IOP elevation of ≥ 10 mmHg. Thus, a cumulative total of 9 subjects (69%) had IOP elevations of at least 5 mmHg and could be classified as moderate to high steroid responders. This model should become useful as a productive source of subjects for studies evaluating the effect on IOP of new ocular stero

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.35

年代:1993

数据来源: MAL

摘要:

ABSTRACTThe objective of this study was to determine the relative efficacy of various formulations in maximizing the ratio of ocular to systemic absorption of topically applied atenolol following solution instillation in the pigmented rabbit. Formulations of various pH's and tonicities and containing various preservatives and polymers were tested. Ocular absorption was determined by monitoring atenolol concentrations in various anterior segment tissues at 30 min following solution instillation, while systemic absorption was determined by monitoring the time course of atenolol concentration over 480 min. Reversed phase HPLC was the analytical methodology. All formulations except those containing 0.025% benzalkonium chloride or 0.5% EDTA showed similar drug concentration vs. time profiles in plasma, attaining a peak concentration of 30-50 ng/ml at about 100 min. For benzalkonium chloride and EDTA, there was an undesirable increase in systemic absorption, although ocular absorption was also increased. By contrast, lowering the solution tonicity to 80 mOsm/kg increased the ratio of aqueous humor to plasma peak concentrations 2 times and the ratio of irisciliary body to plasma peak concentrations 3 times. Incorporation of 3.75% poly(vinyl alcohol) into the formulation afforded yet a larger increase in the iris-ciliary body to plasma drug concentration ratio (52 times.) It may therefore be concluded that, for a hydrophilic drug like atenolol, formulation changes that increase membrane permeability and/or enhance noncorneal drug access may be more promising than those that increase drug residence in the conjunctival sac with respect to maximizing the ratio of ocular to systemic drug absorption.

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.47

年代:1993

数据来源: MAL

摘要:

ABSTRACTThe effect of ascorbic acid 2-O-α-glucoside (AA-2G) on hydrocortisone (HC)-induced lens opacity in developing chick embryo was examined and compared with those of ascorbic acid (AsA) and ascorbic acid 2-phosphate (AA-2P). The opacity was dose-dependently inhibited by a single administration of 10 or 20 μmol/egg of AA-2G and by three repeated administrations of 1, 3 or 10 μmol/egg of AA-2G. AA-2G was the most effective among the three compounds. Glucose did not enhance the preventive effect of AsA against HC-induced opacity, and neither dehydro ascorbic acid nor glucose also prevented HC-induced cataract.In the histological study, we observed many small vacuoles in the nuclear region of the opaque lens treated with HC. AA-2G inhibited the formation of such vacuoles, an effect closely correlated with the prevention of cataract formati

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.59

年代:1993

数据来源: MAL

摘要:

ABSTRACTCiprofloxacin is a fluorinated quinolone antibiotic with a broad spectrum of activity against both gram positive and gram negative organisms. Previous studies have indicated that oral or parenteral preparations of ciprofloxacin resulted in therapeutic concentrations in the aqueous humor but intravitreal levels were found to be only marginally higher than the MIC90for gram positive cocci. Toxicity was evaluated following intravitreal doses of ciprofloxacin injected into the mid-vitreous cavity of one eye of pigmented rabbits. As a control, an identical volume of normal saline was injected into the fellow eye. Four doses of ciprofloxacin were studied, 100 μg, 250 μg, 500 μg and 1000 μg. Electroretinograms (ERGs) were recorded prior to injection and 1, 7 and 14 days after injection. These were analyzed as b-wave amplitude ratios between treated and untreated eyes. On ophthalmoscopic examination focal areas of retinitis were observed following injection of both 500 μg and 1000 μg of ciprofloxacin but not at 250 μg. Additionally, ERG amplitude ratios were significantly reduced following the 1000 μg dose. At the 100 or 250 μg ciprofloxacin dose histological sections are comparable with control eyes and appear normal; ERG ratios were unchanged from the baseline level and careful indirect ophthalmoscopic examination revealed no alterations. Pharmacokinetic analysis after single intravitreal injection of 250 μg of ciprofloxacin (N = 3 rabbits/dose) disclosed vitreous fluid levels (μg/ml) of 146 at 0 hr, 77 at 4 hr, 32 at 8 hr, 0.49 at 24 hr and 0.24 at 48 hr. Peak aqueous humor levels of 0.59 μg/ml occurred at 8 hrs after injection and at 48 hrs, 0.09 μg/ml was detected in a

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.69

年代:1993

数据来源: MAL

摘要:

ABSTRACTThe effects of cholecystokinin (CCK) and calcitonin gene-related peptide (CGRP) on ocular blood flow were studied in monkeys using the labelled microsphere method. Intracameral administration of 800 pmole CGRP increased the blood flow significantly in the conjunctiva, ciliary body and sclera. There was no significant change in the choroid and retina. CCK-33 (800 pmole) caused no significant effects on the blood flow in the tissues examined, when compared to the control eyes. A miotic response was however noted, consistent with previous results. Neither peptide caused significant changes in the intraocular pressure. These results suggest that CGRP has a vasodilatory effect in some parts of the monkey eye, whereas CCK-33 is a miotic with no marked effect on ocular blood flow.

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.77

年代:1993

数据来源: MAL

摘要:

ABSTRACTEyedrops of 0.25% insulin plus 0.5% BL-9 or Brij-78 were instilled into rabbit eyes twice a day for 3 months. It was found that the efficacy of insulin to lower the blood glucose concentration and the uptake of insulin into the systemic circulation remained the same throughout the experimental period. No allergic responses or local side effects could be detected, indicating that both insulin and permeation enhancers (BL-9 and Brij-78) are safe for instillation into the eyes for long periods of time. It is concluded that chronic administration of insulin and absorption enhancers into the eyes is a feasible method to replace injections for diabetes treatment.

ISSN:8756-3320    

DOI:10.1089/jop.1993.9.85

年代:1993

数据来源: MAL