Brinzolamide

Brinzolamide
Names
Pronunciationbrin ZOH la mide
Trade namesAzopt, Befardin, others
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
Clinical data
Drug classCarbonic anhydrase inhibitor[1]
Main usesOpen-angle glaucoma[1]
Side effectsBitter taste, blurry vision[2]
Pregnancy
category
    Routes of
    use    		Eye drop
    External links
    AHFS/Drugs.comMonograph
    US NLMBrinzolamide
    MedlinePlusa601233
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • US: ℞-only
    • EU: Rx-only
    Pharmacokinetics
    BioavailabilityAbsorbed systemically, but below detectable levels (less than 10 ng/mL)
    Protein binding~60%
    Elimination half-life111 days
    ExcretionKidney (60%)
    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 checkY
    • Key:HCRKCZRJWPKOAR-JTQLQIEISA-N checkY

    Brinzolamide, sold under the brand name Azopt among others, is a medication used to treat glaucoma, specifically open-angle glaucoma.[1] It is often used together with beta blockers or prostaglandin analogues.[2] It is used as an eye drop.[1]

    Common side effects include a bitter taste in the mouth and temporary blurry vision.[2] Safety in pregnancy is unclear.[4] It is a carbonic anhydrase inhibitor, which decreases the production of aqueous humour.[1][2]

    Brinzolamide was approved for medical use in the United States in 1998 and Europe in 2000.[1][2] Generic versions were approved in 2020.[5] In the United Kingdom 5 ml costs the NHS about £3 as of 2021.[6] This amount in the United States is about 47 USD.[7]

    Medical uses

    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.

    Dosage

    It is used as one drop 3 times per day.[4]

    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

    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.

    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).

    Combinations

    Combination 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.[8]

    Combination with brimonidine

    The combination of brinzolamide with brimonidine is marketed under the trade name Simbrinza.[9][10] This combination may be more effective than either medication alone.[9][10]

    References

    1. 1 2 3 4 5 6 "Brinzolamide Monograph for Professionals". Drugs.com. Archived from the original on 24 January 2021. Retrieved 11 January 2022.
    2. 1 2 3 4 5 "Azopt". Archived from the original on 29 April 2021. Retrieved 11 January 2022.
    3. ↑ "Brinzolamide ophthalmic (Azopt) Use During Pregnancy". Drugs.com. 16 May 2019. Archived from the original on 28 November 2020. Retrieved 17 August 2020.
    4. 1 2 "Brinzolamide". Archived from the original on 19 April 2021. Retrieved 11 January 2022.
    5. ↑ Research, Center for Drug Evaluation and (23 February 2021). "2020 First Generic Drug Approvals". FDA. Archived from the original on 26 September 2021. Retrieved 11 January 2022.
    6. ↑ BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1226. ISBN 978-0857114105.
    7. ↑ "Brinzolamide Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 2 October 2016. Retrieved 11 January 2022.
    8. ↑ Croxtall JD, Scott, LJ. Archived 2011-10-08 at the Wayback Machine.Drugs&Aging 2009;26(5):437-446. doi:10.2165/00002512-200926050-00007.
    9. 1 2 "Simbrinza EPAR". European Medicines Agency. Archived from the original on 11 June 2020. Retrieved 11 June 2020.
    10. 1 2 "Simbrinza- brinzolamide/brimonidine tartrate suspension/ drops". DailyMed. 9 September 2019. Archived from the original on 11 June 2020. Retrieved 11 June 2020.
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