Ocular Penetration of Cyclosporine A in the Rat Eye

BenEzra, David; Maftzir, Genia

doi:10.1001/archopht.1990.01070060132063

Cited by 56 publications

(35 citation statements)

References 9 publications

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“…It appears that the level of immunosuppression is not always sufficient (BenEzra and Maftzir 1990, Minguez et al 1992, Gratzek et al 1995, Althaus et al 1996, Tran 1997, Heiligenhaus and Steuhl 1999, Zheng et al 2002. Several in vitro and in vivo studies have been performed to evaluate the distribution of cyclosporine A in the eye after suprachoroidal implantation of a cyclosporine A drug delivery device.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the low rate of penetration of topically applied cyclosporine A drops the concentration of the drug in the anterior chamber of the eye is low. The topical use is still the preferred method of application, even though it only yields a low concentration of cyclosporine A in the eye (BenEzra et al 1986, BenEzra and Maftzir 1990, Bleik and Tabbara 1991, Holland et al 1993, Althaus et al 1996, Dua et al 1996, Secchi et al 1997, Tran 1997, Williams 1997, Acheampong et al 1999, Heiligenhaus and Steuhl 1999, Hingorani et al 1999, Braun 2007.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical experience and long-term outcome after subscleral insertion of a cyclosporine A drug delivery device in horses with immune-mediated keratitis

Töth¹,

Huthmann²,

Hollerrieder³

2011

PHK

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SummaryThe purpose of this study was to determine the efficacy and duration of effect of a subscleral cyclosporine A implant in horses with immune-mediated keratitis (IMMK). The study at hand describes the cases of fifteen horses with mature IMMK that were presented to the Tierklinik Hochmoor for further treatment. In theses horses, a cyclosporine A drug delivery device was placed subsclerally adjacent to the suprachoroidal space under general anesthesia. Follow-up was evaluated for up to 53 months duration after implant placement. Objective assessment showed an improvement in 66.7% of patients. Four of the patients suffered a recurrence of symptoms. This study yields promising results for the long-term treatment of IMMK in horses. Sport horses and patients suffering from frequently recurring episodes of IMMK could benefit greatly from this alternative treatment method.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical experience and long-term outcome after subscleral insertion of a cyclosporine A drug delivery device in horses with immune-mediated keratitis

Töth¹,

Huthmann²,

Hollerrieder³

2011

PHK

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“…Besides oral and intravenous administration, intraperitoneal, subconjunctival and retrobulbar applications have been reported in animal studies [22,23]. Recently, successful results have been reported after local CsA application in high-risk keratoplasty [24], ligneous conjunctivitis [25], vernal conjunctivitis [26], atopic keratoconjunctivitis [6], Mooren's ulcer [27], secondary Sjögren syndrome [28] and keratoconjunctivitis sicca [29].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Cyclosporin A on Cultured Rabbit Subconjunctival Fibroblast Proliferation

Bağcı

Yücel²,

Duranoğlu³

1999

Ophthalmologica

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The aim of this study was to examine the possible effects of local application of a potent immunosuppressive drug, cyclosporin A (CsA), on fibroblast proliferation in vitro. Rabbit subconjunctival fibroblasts were cultured and incubated with varying doses of CsA (from 0.5 to 5%). Growth inhibition curves were obtained, and cell attachment and reversibility of drug-induced growth inhibition were studied. None of the doses stimulated fibroblast proliferation. CsA inhibited fibroblast proliferation depending on the dose and duration of application. Also, drug-induced growth inhibition decreased depending on dose and duration of application. While the dosage which led to 50% inhibition was found to be 7.2 mg/ml, 4% and higher doses had toxic effects.

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“…The P-gp substrate cyclosporine A administered orally to humans (BenEzra et al, 1990), rabbits (BenEzra and Maftzir, 1990a), and rats (BenEzra and Maftzir, 1990b) at therapeutic doses is not detected in the aqueous humor or vitreous, except when the ocular barriers are disrupted by inflammation, suggesting that P-gp-mediated efflux plays an important role in drug absorption across the ocular barriers after systemic administration. Indeed, after intravenous administration of the P-gp substrates quinidine, digoxin, and verapamil, their aqueous humor uptake index values (concentration of drug in aqueous humor/ concentration of drug in blood) are lower than predicted based on their log D 7.4 values, but are increased in the presence of P-gp inhibitors (Toda et al, 2011;Fujii et al, 2014).…”

Section: In Vivo Evidence For Drug Transporter Function In the Eyementioning

confidence: 99%

Drug Transport by the Blood-Aqueous Humor Barrier of the Eye

Lee

Pelis

2016

Drug Metabolism and Disposition

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The ocular barriers (cornea, blood-retinal barrier, and blood-aqueous humor barrier) make treating eye diseases with therapeutic drugs challenging. The tight capillary endothelium of the iris and the ciliary body epithelium form the blood-aqueous humor barrier. The iris and ciliary body (iris-ciliary body) express a variety of drug transporters in the ATP-binding cassette and solute carrier (SLC) families. ATPbinding cassette family drug transporters that are present in the irisciliary body include P-glycoprotein, breast cancer resistance protein, and several multidrug resistance-associated proteins. SLC family drug transporters that are present in the iris-ciliary body include organic anion transporters, organic anion transporting polypeptides, bile acid transporters (apical sodium-dependent bile salt transporter and sodium taurocholate cotransporter), organic cation transporters (novel organic cation transporter and multidrug and toxin extrusion transporter) and peptide transporters. Freshly dissected iris-ciliary body preparations actively accumulate a variety of substrates of SLC drug transporters that are expressed in the tissue. The ciliary body in vitro supports active transport in the aqueous humor-to-blood direction of several substrates of organic anion transporters and multidrug resistance-associated proteins, consistent with the subcellular localization of these transporters in the ciliary body epithelium. In vivo data suggest that drug transporters in the iris-ciliary body reduce the permeation of drugs in the direction of blood-toaqueous humor, thereby reducing ocular drug bioavailability, and are also involved in active drug elimination from the aqueous humor. An understanding of the influence on pharmacokinetics of drug transporters in the blood-aqueous humor barrier should help improve drug delivery and efficacy in the eye.

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Ocular Penetration of Cyclosporine A in the Rat Eye

Cited by 56 publications

References 9 publications

Clinical experience and long-term outcome after subscleral insertion of a cyclosporine A drug delivery device in horses with immune-mediated keratitis

Clinical experience and long-term outcome after subscleral insertion of a cyclosporine A drug delivery device in horses with immune-mediated keratitis

The Effect of Cyclosporin A on Cultured Rabbit Subconjunctival Fibroblast Proliferation

Drug Transport by the Blood-Aqueous Humor Barrier of the Eye

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