Pharmacokinetics and Tissue Distribution of Pilocarpine After Application to Eyelid Skin of Rats

See, Gerard Lee; Sagesaka, Ayano; Todo, Hiroaki; Wierzba, Konstanty; Sugibayashi, Kenji

doi:10.1016/j.xphs.2019.04.012

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…Limited information is available regarding its ocular pharmacological properties. In 2019, See et al reported the pharmacokinetics and tissue distribution of topically instilled pilocarpine in vivo [ 282 ]. In this study, the authors aimed to comparatively evaluate the pharmacokinetics of two delivery methods for the drug: topical eyedrop instillation vs. topical eyelid application.…”

Section: Glaucoma Therapeuticsmentioning

confidence: 99%

“…The concentrations of the pilocarpine solution used in this study, however, are not equal. Their results showed that the topical instillation of the eyedrops resulted in rapid drug penetration into the eye by absorption across the cornea from the precorneal tear film [ 282 ]. Fast elimination of the drug at the application site was also reported, noticeably affecting the drug delivery efficiency of the eyedrop formulation [ 282 ].…”

Section: Glaucoma Therapeuticsmentioning

confidence: 99%

See 1 more Smart Citation

Chemical Insights into Topical Agents in Intraocular Pressure Management: From Glaucoma Etiopathology to Therapeutic Approaches

Patton,

Lee

2024

Pharmaceutics

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Glaucoma encompasses a group of optic neuropathies characterized by complex and often elusive etiopathology, involving neurodegeneration of the optic nerve in conjunction with abnormal intraocular pressure (IOP). Currently, there is no cure for glaucoma, and treatment strategies primarily aim to halt disease progression by managing IOP. This review delves into the etiopathology, diagnostic methods, and treatment approaches for glaucoma, with a special focus on IOP management. We discuss a range of active pharmaceutical ingredients used in glaucoma therapy, emphasizing their chemical structure, pharmacological action, therapeutic effectiveness, and safety/tolerability profiles. Notably, most of these therapeutic agents are administered as topical formulations, a critical aspect considering patient compliance and drug delivery efficiency. The classes of glaucoma therapeutics covered in this review include prostaglandin analogs, beta blockers, alpha agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, and miotic (cholinergic) agents. This comprehensive overview highlights the importance of topical administration in glaucoma treatment, offering insights into the current state and future directions of pharmacological management in glaucoma.

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Section: Glaucoma Therapeuticsmentioning

confidence: 99%

Section: Glaucoma Therapeuticsmentioning

confidence: 99%

Chemical Insights into Topical Agents in Intraocular Pressure Management: From Glaucoma Etiopathology to Therapeutic Approaches

Patton,

Lee

2024

Pharmaceutics

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“…The peak plasma concentration (Cmax) was determined directly from plasma or brain concentration-time curves. The area under the plasma or brain concentration-time curve (AUC0-8) was calculated using trapezoidal rule [20][21][22]. Drug targeting efficiency percentage (DTE)…”

Section: Tissue Distribution Studies Of Tl Formulationsmentioning

confidence: 99%

Enhanced nose-to-brain delivery of tranilast using liquid crystal formulations

See

Arce

Dahlizar

et al. 2020

Journal of Controlled Release

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Highlights• Intranasal delivery of tranilast was enhanced by MGE and GMO liquid crystals • Biodistribution of administered LC formulations was visualized by micro-computed tomography tandem in vivo imaging systems • MGE and GMO formed liquid crystal structures with formulation characteristics supporting brain uptake of lipophilic drugs ABSTRACT Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10-to 12-fold and 2-to 2.4-fold, respectively, compared with TL solution.The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.

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“…Several works have validated the capacity of the eyelids to support the delivery of drugs into the ocular tissues. [2][3][4][5] Our previous work showed that topical application of drugs onto the eyelids yielded high absorption in the conjunctiva and the eyeball, which was mainly be attributed to the thin skin barrier, the stratum corneum, and lower amounts of neutral lipids in the eyelid skin. 5) Tranilast, anthranilic acid, is a lipophilic drug which have wide applications against ocular conditions such as allergic conjunctivitis, 6) prevention of post-operative adhesion after strabismus surgery, 7) treatment of corneal allergic inflammation, 8) and prevention of fibrous opacification of the posterior lens capsule after cataract extraction 9) among others.…”

Section: Introductionmentioning

confidence: 99%

Prolonged Distribution of Tranilast in the Eyes after Topical Application onto Eyelid Skin

See

Arce

Itakura

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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Tranilast, a lipophilic drug with various ophthalmic applications, was used as a model drug to establish the possibility of delivering lipophilic drugs through the eyelid skin. Pharmacokinetics and tissue distribution studies were conducted employing three application methods (topical application onto eyelid skin, eye drops, and intravenous injection in rats) to broaden the significance of delivering drugs through the eyelids.A two-compartment open model analysis was used for intravenous route while a non-compartmental evaluation was used for topical applications to estimate the pharmacokinetic parameters. Eyelid skin application, eye drops, and intravenous administration had mean residence times (MRTs) of 8.07, 1.79, and 3.25 h in the eyeball and 10.8, 1.29, and 2.97 h in the conjunctiva, correspondingly. In the eyeball, topical application of tranilast onto the eyelids corresponded to a 4.5-and 2.5-fold higher MRT compared with eye drops and intravenous administration, respectively. An 8.4-or 3.6-fold higher MRT was observed in the conjunctiva after topical application compared with eye drops or intravenous administration, respectively. This indicated a gradual penetration of tranilast into the eyeball and conjunctiva, subsequently a slow elimination from these target tissues.

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Pharmacokinetics and Tissue Distribution of Pilocarpine After Application to Eyelid Skin of Rats

Cited by 8 publications

References 19 publications

Chemical Insights into Topical Agents in Intraocular Pressure Management: From Glaucoma Etiopathology to Therapeutic Approaches

Chemical Insights into Topical Agents in Intraocular Pressure Management: From Glaucoma Etiopathology to Therapeutic Approaches

Enhanced nose-to-brain delivery of tranilast using liquid crystal formulations

Prolonged Distribution of Tranilast in the Eyes after Topical Application onto Eyelid Skin

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