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Anti-inflammatory action and intraocular kinetics of bromfenac in anterior uveitis depending on the composition of topical formulation

https://doi.org/10.21516/2072-0076-2024-17-4-70-77

Abstract

Purpose: a comparative study of the main characteristics of the anti-inflammatory effect of the ophthalmic dosage form (ODF) of bromfenac — the drug Broxinac and analogues, their local bioavailability, biodistribution and intraocular pharmacokinetics during the inflammatory process in the anterior segment of the rabbit eye.

Material and methods. The studies were performed on 40 sexually mature male rabbits of the “Soviet Chinchilla” breed with an experimental model of carrageenan anterior uveitis. The anti-inflammatory and local irritant effect on the cornea, bioavailability and intraocular pharmacokinetics in the anterior chamber humor of ODF - bromfenac drops with various auxiliary components when instilled into the conjunctival sac were determined.

Results. Broxinac, containing 0.05 mg/ml benzalkonium chloride as an auxiliary substance, exhibits more pronounced anti-inflammatory properties than existing analogues containing benzalkonium chloride at a concentration of 0.01 mg/ml or not containing it at all. The drug does not cause a local irritant effect when administered every 12 hours for 10 days 1 drop into the conjunctival sac of the eye of an awake rabbit, only minor signs of irritation in the form of closing of the eyelids in some rabbits were noted. When using comparison drugs containing 0.01 mg of the aforementioned preservative, the severity of the local irritant reaction fluctuated in a fairly wide range: from moderate to pronounced. It was established that the dosing form of Broxinac creates high peak concentrations in the anterior chamber humor and vitreous body, which remain within the therapeutic limits for at least 12 hours regardless of the presence of uveitis, with a half-life from the anterior chamber humor, depending on the presence of pathology, from 79 to 89 minutes.

Conclusion. The ability of auxiliary components to change the pharmacology of the dosing form is the basis for optimizing the local bioavailability and pharmacodynamics of bromfenac as the active substance of the drug Broxinac. An increase in the concentration of benzalkonium chloride to 0.05 mg / ml (which is 5 times higher than that of the selected analogues) facilitates the passage of bromfenac through the tissue barrier of the eye and prevents presystemic elimination.

About the Authors

E. V. Blinova
Sechenov Medical University
Russian Federation

Ekaterina V. Blinova — Dr. of Med. Sci., professor, professor of the department of clinical pharmacology and internal diseases propaedeutic, N.V. Sklifosovsky Institute of Clinical Medicine.

8/2, Trubetskaya St., Moscow, 119991



P. A. Lyabushev
Sechenov Medical University
Russian Federation

Petr A. Lyabushev — PhD student, department of clinical pharmacology and internal diseases propaedeutic, N.V. Sklifosovsky Institute of Clinical Medicine.

8/2, Trubetskaya St., Moscow, 119991



E. A. Litvin
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Russian Federation

Evgeny A. Litvin — Cand. of Biol. Sci., researcher of laboratory of pharmacology healthcare technology assessment.

8/2, Trubetskaya St., Moscow, 119991



D. S. Blinov
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Russian Federation

Dmitry S. Blinov — Dr. of Med. Sci., head of the laboratory of pharmacology healthcare technology assessment.

8/2, Trubetskaya St., Moscow, 119991



A. A. Galchin
Moscow Engineering and Physical University
Russian Federation

Alexander A. Galchin — Cand. of Med. Sci., deputy director of the engineering and physics institute of biomedicine.

31, Kashirskoe Hgwy, Moscow, 115409



M. V. Shikh
Bauman Moscow State Technical University
Russian Federation

Maksim V. Shikh — Master.

5, Bldg. 1, 2nd Baumanskaya St., Moscow, 105005



I. S. Struts
Sechenov Medical University
Russian Federation

Ivar S. Struts — 4th year student.

8/2, Trubetskaya St., Moscow, 119991



K. D. Blinov
Sechenov Medical University
Russian Federation

Kirill D. Blinov — 2th year student.

8/2, Trubetskaya St., Moscow, 119991



S. D. Yudina
Sechenov Medical University
Russian Federation

Sof’ya D. Yudina — 2th year student.

8/2, Trubetskaya St., Moscow, 119991



O. V. Vasilkina
Moscow Engineering and Physical University
Russian Federation

Olga V. Vasilkina — Cand. of Med. Sci., associate professor, department of fundamental medicine.

31, Kashirskoe Hgwy, Moscow, 115409



S. E. Zotov
Sechenov Medical University
Russian Federation

Sergey E. Zotov — 5th year student.

8/2, Trubetskaya St., Moscow, 119991



E. V. Shikh
Sechenov Medical University
Russian Federation

Evgeniia V. Shich — Dr. of Med. Sci., professor, head of the department of clinical pharmacology and internal diseases propaedeutic, N.V. Sklifosovsky Institute of Clinical Medicine.

8/2, Trubetskaya St., Moscow, 119991



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Review

For citations:


Blinova E.V., Lyabushev P.A., Litvin E.A., Blinov D.S., Galchin A.A., Shikh M.V., Struts I.S., Blinov K.D., Yudina S.D., Vasilkina O.V., Zotov S.E., Shikh E.V. Anti-inflammatory action and intraocular kinetics of bromfenac in anterior uveitis depending on the composition of topical formulation. Russian Ophthalmological Journal. 2024;17(4):70-77. (In Russ.) https://doi.org/10.21516/2072-0076-2024-17-4-70-77

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ISSN 2072-0076 (Print)
ISSN 2587-5760 (Online)