Drug transport in corneal epithelium and blood–retina barrier: Emerging role of transporters in ocular pharmacokinetics

Mannermaa, Eliisa; Vellonen, Kati‐Sisko; Urtti, Arto

doi:10.1016/j.addr.2006.07.024

Cited by 294 publications

(219 citation statements)

References 203 publications

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“…4 Despite the restriction offered by the corneal epithelium, transcorneal penetration is the major route of entry for drugs from tears to AH. 5 Hence, cationic drugs may utilize some uptake transporters for their permeation across biological membranes.…”

Section: Discussionmentioning

confidence: 99%

“…13 Many of the pharmacologically important drugs in ophthalmic practice are substrates of OCT, thereby their bioavailability is getting altered. 4,14 Various studies in humans and animals showed the modulation in the ocular penetration of various OC. Additional administration of diclofenac sodium significantly increased the mean intraocular pressure (IOP) in patients undergoing latanoprost therapy.…”

Section: Introductionmentioning

confidence: 99%

“…2 Studies indicate that presence of a physiological protective mechanism like transporter proteins may be responsible for the uptake or altered penetration of drugs across the cornea. [3][4][5] Most of the endogenous amines having a physiologically important role are organic cations (OC) and carry a positive charge, so they are unable to permeate across the cornea. Therefore, a specialized transport process has been reported to exist in the conjunctival and corneal epithelial cells involved in the regulation of the transport of various endogenous amines such as epinephrine, dopamine, histamine, and serotonin from tear fluid.…”

Section: Introductionmentioning

confidence: 99%

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Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

Nirmal

Singh

Biswas

et al. 2013

Eye

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

Nirmal

Singh

Biswas

et al. 2013

Eye

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“…Efflux transporters tend to reduce cellular bioavailability by transporting drugs out of the cell. Key efflux transporters associated with ocular tissues are P-glycoprotein (P-gp) and multidrug resistance protein (MRP), which belong to the ATP-binding cassette (ABC) superfamily (Eytan and Kuchel 1999;Dey et al 2003;Mannermaa et al 2006). P-gp effluxes lipophilic drugs and prevents drug accumulation in the cells.…”

Section: Transporters In the Eyementioning

confidence: 99%

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

Narayanan

Kuppermann

2016

Handbook of Experimental Pharmacology

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“…The presence of Pglycoprotein efflux transporters, cationic/anionic transporters, and other transporters in the BRB that resist the entry of systemically given substrates is well documented. [5][6][7] Hence, for any predictable outcome in retinal neuroprotection, the ocular pharmacokinetic profile of the drug needs to be explored before initiating a clinical trial.…”

mentioning

confidence: 99%

Closed Gateways — Can Neuroprotectants Shield the Retina in Glaucoma?

Velpandian

2010

Drugs R D

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Neuroprotection for glaucoma is a therapeutic approach that aims to prevent optic nerve damage or cell death. An appropriate drug that reaches an adequate concentration across the blood retinal barrier is expected to shield the retina in glaucoma. Several in vitro and in vivo attempts in experimental models indicate the possibility of successful neuroprotection. However, clinical trials might not show the same level of neuroprotection as a result of subtherapeutic concentrations of the drug in the eye. The study by Zhong et al. in this issue of Drugs in R&D could not attribute the observed improvement in visual field indices to any one of the individual active constituents of Erigeron breviscapus (vant.) Hand. Mazz. (EBHM). One of the major constituents of EBHM is scutellarin, which is known to have poor oral bioavailability and an unclear ability to penetrate inside the eye. Therefore, before recognizing EBHM as a neuroprotectant in glaucoma for further clinical studies and practice, its active constituents and their pharmacokinetics (systemic as well as ocular) need to be explored.Neuroprotection as a pharmacological strategy to shield retinal ganglion cell death has been a popular approach adopted by many researchers. Yet, its effectiveness in preventing retinal ganglion cell death and thereby preserving vision in patients with primary open-angle glaucoma has not been demonstrated. [1] Mitochondria are abundant in the unmyelinated part of the retinal ganglion cell axons to meet the higher energy demand for nerve conduction and for the maintenance of optimum neuronal function. [2] Ischemia to the optic nerve head region can cause ganglion cell death at different rates. Therefore, effective intraocular pressure (IOP) control and blocking intracellular death triggers are both viable options. The right pharmacologic agent with a meaningful intraocular penetration would rationalize the neuroprotection strategy in glaucoma.For the last three decades, several attempts have been made to establish a successful neuroprotectant for glaucoma using various in vitro and in vivo models. A comprehensive PubMed search with the MeSH terms ''glaucoma'' and ''neuroprotection'' revealed the following compounds, factors and plant extracts: NMDA receptor antagonists (memantine, dexanabinol), an a2-adrenergic receptor agonist (brimonidine), an a 1 -and b-adrenergic receptor antagonist with a nitric oxide donor (nipradilol), an angiotensin II type 1 receptor blocker (candesartan), a prostaglandin-related compound (tafluprost), calcium channel blockers (nilvadipine and cilnidipine), a sodium channel blocker (phenytoin), a dual COMMENTARY Drugs R D 2010; 10 (2): 93-96

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Drug transport in corneal epithelium and blood–retina barrier: Emerging role of transporters in ocular pharmacokinetics

Cited by 294 publications

References 203 publications

Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

Potential pharmacokinetic role of organic cation transporters in modulating the transcorneal penetration of its substrates administered topically

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

Closed Gateways — Can Neuroprotectants Shield the Retina in Glaucoma?

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