Brinzolamide

Brinzolamide (trade names Azopt, Alcon Laboratories, Befardin,[2] Fardi Medicals,[3] ) is a carbonic anhydrase inhibitor used to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Brinzolamide
Clinical data
Pronunciationbrin ZOH la mide
Trade namesAzopt, Befardin
AHFS/Drugs.comMonograph
MedlinePlusa601233
License data
Pregnancy
category
Routes of
administration		Ophthalmic
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetic data
BioavailabilityAbsorbed systemically, but below detectable levels (less than 10 ng/mL)
Protein binding~60%
Elimination half-life111 days
ExcretionKidney (60%)
Identifiers
IUPAC name
  • (5R)-5-ethylamino-3-(3-methoxypropyl)-
    2,2-dioxo-2λ6,9-dithia-
    3-azabicyclo[4.3.0]nona-7,10-diene-
    8-sulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.149.376
Chemical and physical data
FormulaC12H21N3O5S3
Molar mass383.50 g·mol−1
3D model (JSmol)
SMILES
  • O=S(=O)(c1sc2c(c1)[C@@H](NCC)CN(CCCOC)S2(=O)=O)N
InChI
  • InChI=1S/C12H21N3O5S3/c1-3-14-10-8-15(5-4-6-20-2)23(18,19)12-9(10)7-11(21-12)22(13,16)17/h7,10,14H,3-6,8H2,1-2H3,(H2,13,16,17)/t10-/m0/s1 Y
  • Key:HCRKCZRJWPKOAR-JTQLQIEISA-N Y
  (verify)

Brinzolamide was approved as a generic medication in the United States in November 2020.[4]

Chemistry

Brinzolamide is a carbonic anhydrase inhibitor (specifically, carbonic anhydrase II). Carbonic anhydrase is found primarily in erythrocytes (but also in other tissues including the eye). It exists as a number of isoenzymes, the most active of which is carbonic anhydrase II (CA-II).

Indications

Use for the treatment of open-angle glaucoma and raised intraocular pressure due to either excess aqueous humor production or inadequate drainage of the humor via the trabecular meshwork.

Pharmacodynamics

Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion and thus lowers the intraocular pressure in the anterior chamber, presumably by reducing the rate of formation of bicarbonate ions with subsequent reduction in sodium and fluid transport; this may alleviate the effects of open-angle glaucoma.

Pharmacokinetics

Absorption

The recommended frequency for topical application is two times per day. Following ocular instillation, the suspension is systemically absorbed to some degree; however the plasma concentrations are low and generally below the limits of detection (less than 10 ng/mL) due to extensive binding by tissues and erythrocytes. Oral administration is less-favored due to variable absorption from the stomach mucosa and an increased side-effect profile versus ophthalmic administration.

Distribution

The compound is fairly well protein-bound (60%), but adheres extensively to the carbonic anhydrase-containing erythrocytes. Due to the abundance of readily-bound erythrocytes and minimal known metabolism, Brinzolamide's whole blood half-life is very long (111 days).

Metabolism

While definitive sites of metabolism have not been firmly established, there are several metabolites worthy of note. N-Desethylbrinzolamide is an active metabolite of the parent compound, and thus exhibits carbonic anhydrase inhibitory activity (largely carbonic anhydrase-I, when in the presence of Brinzolamide) and also accumulates in the erythrocytes. However, Brinzolamide's other known metabolites (N-Desmethoxypropylbrinzolamide and O-Desmethylbrinzolamide) either have no activity or their activity is currently unknown.

Excretion

Brinzolamide is excreted primarily unchanged (60%) in the urine, although the renal clearance rate has not been definitively determined. N-Desethylbrinzolamide is also found in the urine along with lower concentrations of the inactive metabolites, N-Desmethoxypropylbrinzolamide and O-Desmethylbrinzolamide; exact levels have not been definitively determined.

Cautions

Side effects
  • Common, but mild: blurred vision; bitter, sour, or unusual taste; itching, pain, watering, or dryness of the eyes; feeling that something is in the eye; headache; runny nose
  • Rare, but serious: fast or irregular heartbeat; fainting; skin rash, hives, or itching; severe eye irritation, redness, or swelling; swelling in the face, lips, or throat; wheezing or trouble breathing

Precautions

Combinations

With timolol

The combination of brinzolamide with timolol is marketed under the trade name Azarga. This combination may be more effective than either medication alone.[5]

With brimonidine

The combination of brinzolamide with brimonidine is marketed under the trade name Simbrinza.[6][7] This combination may be more effective than either medication alone.[6][7]

References
  1. "Brinzolamide ophthalmic (Azopt) Use During Pregnancy". Drugs.com. 16 May 2019. Retrieved 17 August 2020.
  2. "Brinzolamide". Fardi Medicals (in Georgian). Archived from the original on 2015-07-06. Retrieved 2015-07-04.
  3. "Befardin" (PDF) (in Georgian). Archived from the original (PDF) on 2015-07-05. Retrieved 2015-07-04.
  4. "First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). Retrieved 13 February 2021.
  5. Croxtall JD, Scott LJ (2009). "Brinzolamide/timolol: in open-angle glaucoma and ocular hypertension". Drugs & Aging. 26 (5): 437–46. doi:10.2165/00002512-200926050-00007. PMID 19552495.
  6. "Simbrinza EPAR". European Medicines Agency. Retrieved 11 June 2020.
  7. "Simbrinza- brinzolamide/brimonidine tartrate suspension/ drops". DailyMed. 9 September 2019. Retrieved 11 June 2020.

Further reading
  • "Brinzolamide". Drug Information Portal. U.S. National Library of Medicine.
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