Crossover Randomized Study of Pharmacologic Effects of Ripasudil–Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine

• Published in: Advances in therapy 2023-08, Vol.40 (8), p.3559-3573
• Main Authors: Tanihara, Hidenobu, Yamamoto, Tetsuya, Aihara, Makoto, Koizumi, Noriko, Minami, Hiroomi, Kojima, Satoshi, Isobe, Tomoyuki, Kanazawa, Mizuho, Suganami, Hideki
• Format: Article
• Language: English
• Subjects: Adult; Antihypertensive Agents - therapeutic use; Brimonidine Tartrate - pharmacology; Brimonidine Tartrate - therapeutic use; Cardiology; Endocrinology; Endothelial Cells; Glaucoma, Open-Angle - drug therapy; Humans; Hyperemia - chemically induced; Hyperemia - drug therapy; Internal Medicine; Intraocular Pressure; jRCT; jRCT2080225220; Male; Medicine; Medicine & Public Health; Ocular Hypertension - drug therapy; Oncology; Ophthalmic Solutions - therapeutic use; Original Research; Pharmacology/Toxicology; Prospective Studies; Quinoxalines - adverse effects; Rheumatology
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/s12325-023-02534-w

Introduction Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil–brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α 2 -adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components—ripasudil or brimonidine. Methods This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics. Results Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P