Ripasudil

Ripasudil Uses, Dosage, Side Effects, Food Interaction and all others data.

Ripasudil, as hydrochloride hydrate (K-115), is a specifc Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor used for the treatment of glaucoma and ocular hypertension. It was first approved for treatment in Japan in September 2014. This medication is available in the form of a 0.4% eye drop solution under the brand name Glanatec. Ripasudil is a well tolerated medication that is used when other drugs have been proven to be non-effective or cannot be administered.

Ripasudil has high intraocular permeability and works by decreasing intraocular pressure (IOP) in a dose-dependent manner and increasing flow facility. The maximum reduction of IOP occurs after 1 to 2 hours.

Ripasudil
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Dosage
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Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
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Trade Name	Ripasudil
Generic	Ripasudil
Ripasudil Other Names	Ripasudil
Type
Formula	C₁₅H₁₈FN₃O₂S
Weight	Average: 323.39 Monoisotopic: 323.110376169
Protein binding	The plasma protein binding rate of Ripasudil is 55.4-59.8%
Groups	Experimental
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Ripasudil is a rho kinase inhibitor indicated to treat ocular hypertension and open-angle glaucoma.

Ripasudil has been proven to be effective in the twice daily treatment of glaucoma and ocular hypertension. It is currently in studies to be approved for both diabetic retinopathy and diabetic macular oedema.

Ripasudil is also used to associated treatment for these conditions: Ocular Hypertension, Open-angle Glaucoma (OAG)

How Ripasudil works

Ripasudil is a highly selective and potent Rho-associated coiled/coil-containing kinase protein (ROCK) inhibitor. Rho-kinase (ROCK) is an effector protein of Rho which binds with Rho to form a Rho/Rho-kinase complex. This complex then regulates many physiological functions including smooth muscle contractions, chemotaxis, neural growth and gene expression. ROCK comes in 2 isoforms: ROCK-1 and ROCK-2 and these two isoforms are distributed widely in our tissues including ocular tissues such as the iris, retina, trabecular meshwork and ciliary muscles. Atypical regulation of ROCK levels is involved in the pathogenesis of diseases such as glaucoma, ocular hypertension, cataracts and other retinal disorders.

Ripasudil acts as very highly selective and potent inhibitor with an IC50 of Ripasudil with ROCK-1 of 0.051 umol/L and with ROCK-2 of 0.019 umol/L. ROCK inhibitors have efficacy in reducing IOP by acting on the trabecular meshwork in the eye directly to increase conventional outflow through the Schlemm’s canal. Ripasudil will inhibit ROCK and induce cytoskeletal changes including the retraction and rounding of cell bodies and cause disruption of actin bundles in this trabecular meshwork. This can reduce the compaction of trabecular meshwork tissue and eventually result in increased aqueous outflow in the eye and reduced resistance to fluid flow.

Thus, Ripasudil is effective by inducing cytoskeletal changes which are depending on ROCK inhibition. Ripasudil decreases IOP by increasing outflow facility along with modulating the behavior of trabecular meshwork cells and Schlemm’s canal endothelial (SCE) cell permeability along with a disruption of the tight junction.

When Ripasudil is used in combination with prostaglandin analogues it results in increased uveoscleral outflow and when used in combination with beta blockers it results in reduced aqueous production.

Toxicity

The most frequent adverse effect of Ripasduil is mild to moderately severe conjunctival hyperemia which was found to cease spontaneously within hours. Mild conjunctival follicles were also reported which also were spontaneously resolved. Other adverse effects include ocular irritation, an abnormal sensation in the eye and conjunctival haemorrhage.

Ripasudil has not been found to have any effects to other receptors and enzymes including serine-threonine protein kinases.