Peringatan Keamanan

A number of case reports demonstrating the capability for bendazac oral and eye drop therapy to cause potential hepatotoxicity via increases in serum transaminases in patients have been documented A39891, A39892, A39869. Moreover, bendazac has also since been discontinued or withdrawn in various international regions due to the possibility and risk of eliciting hepatotoxicity in patients A39893, L4778.

Bendazac

DB13501

small molecule approved withdrawn

Deskripsi

Bendazac is an oxyacetic acid A39863, A39869. Despite possessing anti-inflammatory, anti-necrotic, choleretic, and anti-lipidemic characteristics, most research has revolved around studying and demonstrating the agent's principal action in inhibiting the denaturation of proteins - an effect that has primarily proven useful in managing and delaying the progression of ocular cataracts A39863. A39863. Bendazac, however, has since been withdrawn or discontinued in various international regions due to its capability or risk for eliciting hepatotoxicity A39891, A39892, A39893, L4778 in patients although a small handful of regions may continue to have the medication available for purchase and use either as a topical anti-inflammatory/analgesic cream or eye drop formulation.

Struktur Molekul 2D

Berat 282.299
Wujud -

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The plasma elimination half-life recorded for bendazac is given as 1.7 to 5.2 hours, with a mean of 3.5 hours [A39863, A39869].
Volume Distribusi The volume of distribution documented for bendazac is 0.16 L/kg [A39863, A39869].
Klirens (Clearance) The plasma clearance recorded for bendazac is given as 0.018 to 0.054 L/h/kg with a mean of 0.033 L/h/kg [A39863, A39869].

Absorpsi

Administered as its lysine salt, a 500 mg oral tablet of bendazac is well absorbed into the human body with maximum plasma concentrations Cmax ranging from 35 to 55 mg/L being attained within 0.5 to 1 hour in healthy volunteers after oral administration of a single 500 mg dose A39863, A39869.

Metabolisme

Bendazac is largely eliminated by metabolism, where more than 60% of an administered dose is excreted in the urine as the hydroxylated primary metabolite 5-hydroxybendazac and its glucuronide A39863, A39869, A39900 while up to approximately 15% of a bendazac dose is also excreted in the urine unchanged and as a glucuronide A39863, A39869. Unfortunately, there is little data available regarding the specific enzymes responsible for bendazac's metabolism A39901.

Rute Eliminasi

About 60% of a dose of bendazac is eliminated via the urine as its primary metabolite, 5-hydroxybendazac A39863, A39869. Approximately 15% of a dose is eliminated as unchanged drug and bendazac glucuronide in the urine as wellA39863, A39869.

Interaksi Obat

150 Data
Diclofenac The risk or severity of adverse effects can be increased when Diclofenac is combined with Bendazac.
Flurbiprofen The risk or severity of adverse effects can be increased when Flurbiprofen is combined with Bendazac.
Bromfenac The risk or severity of adverse effects can be increased when Bromfenac is combined with Bendazac.
Nepafenac The risk or severity of adverse effects can be increased when Nepafenac is combined with Bendazac.
Indomethacin The risk or severity of adverse effects can be increased when Indomethacin is combined with Bendazac.
Nabumetone The risk or severity of adverse effects can be increased when Nabumetone is combined with Bendazac.
Tenoxicam The risk or severity of adverse effects can be increased when Tenoxicam is combined with Bendazac.
Celecoxib The risk or severity of adverse effects can be increased when Celecoxib is combined with Bendazac.
Tolmetin The risk or severity of adverse effects can be increased when Tolmetin is combined with Bendazac.
Rofecoxib The risk or severity of adverse effects can be increased when Rofecoxib is combined with Bendazac.
Piroxicam The risk or severity of adverse effects can be increased when Piroxicam is combined with Bendazac.
Fenoprofen The risk or severity of adverse effects can be increased when Fenoprofen is combined with Bendazac.
Valdecoxib The risk or severity of adverse effects can be increased when Valdecoxib is combined with Bendazac.
Sulindac The risk or severity of adverse effects can be increased when Sulindac is combined with Bendazac.
Etodolac The risk or severity of adverse effects can be increased when Etodolac is combined with Bendazac.
Mefenamic acid The risk or severity of adverse effects can be increased when Mefenamic acid is combined with Bendazac.
Naproxen The risk or severity of adverse effects can be increased when Naproxen is combined with Bendazac.
Sulfasalazine The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Bendazac.
Phenylbutazone The risk or severity of adverse effects can be increased when Phenylbutazone is combined with Bendazac.
Meloxicam The risk or severity of adverse effects can be increased when Meloxicam is combined with Bendazac.
Carprofen The risk or severity of adverse effects can be increased when Carprofen is combined with Bendazac.
Diflunisal The risk or severity of adverse effects can be increased when Diflunisal is combined with Bendazac.
Suprofen The risk or severity of adverse effects can be increased when Suprofen is combined with Bendazac.
Salicylic acid The risk or severity of adverse effects can be increased when Salicylic acid is combined with Bendazac.
Meclofenamic acid The risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Bendazac.
Oxaprozin The risk or severity of adverse effects can be increased when Oxaprozin is combined with Bendazac.
Ketoprofen The risk or severity of adverse effects can be increased when Ketoprofen is combined with Bendazac.
Balsalazide The risk or severity of adverse effects can be increased when Balsalazide is combined with Bendazac.
Ibuprofen The risk or severity of adverse effects can be increased when Ibuprofen is combined with Bendazac.
Olsalazine The risk or severity of nephrotoxicity can be increased when Bendazac is combined with Olsalazine.
Lumiracoxib The risk or severity of adverse effects can be increased when Lumiracoxib is combined with Bendazac.
Magnesium salicylate The risk or severity of adverse effects can be increased when Magnesium salicylate is combined with Bendazac.
Salsalate The risk or severity of adverse effects can be increased when Salsalate is combined with Bendazac.
Choline magnesium trisalicylate The risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with Bendazac.
Antipyrine The risk or severity of adverse effects can be increased when Antipyrine is combined with Bendazac.
Tiaprofenic acid The risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Bendazac.
Etoricoxib The risk or severity of adverse effects can be increased when Etoricoxib is combined with Bendazac.
Oxyphenbutazone The risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Bendazac.
Niflumic acid The risk or severity of adverse effects can be increased when Niflumic acid is combined with Bendazac.
Benoxaprofen The risk or severity of adverse effects can be increased when Benoxaprofen is combined with Bendazac.
Zomepirac The risk or severity of adverse effects can be increased when Zomepirac is combined with Bendazac.
Lornoxicam The risk or severity of adverse effects can be increased when Lornoxicam is combined with Bendazac.
Aceclofenac The risk or severity of adverse effects can be increased when Aceclofenac is combined with Bendazac.
Zaltoprofen The risk or severity of adverse effects can be increased when Zaltoprofen is combined with Bendazac.
Azapropazone The risk or severity of adverse effects can be increased when Azapropazone is combined with Bendazac.
Felbinac The risk or severity of adverse effects can be increased when Felbinac is combined with Bendazac.
Parecoxib The risk or severity of adverse effects can be increased when Parecoxib is combined with Bendazac.
Salicylamide The risk or severity of adverse effects can be increased when Salicylamide is combined with Bendazac.
Kebuzone The risk or severity of adverse effects can be increased when Kebuzone is combined with Bendazac.
Isoxicam The risk or severity of adverse effects can be increased when Isoxicam is combined with Bendazac.
Indoprofen The risk or severity of adverse effects can be increased when Indoprofen is combined with Bendazac.
Ibuproxam The risk or severity of adverse effects can be increased when Ibuproxam is combined with Bendazac.
Floctafenine The risk or severity of adverse effects can be increased when Floctafenine is combined with Bendazac.
Fenbufen The risk or severity of adverse effects can be increased when Fenbufen is combined with Bendazac.
Etofenamate The risk or severity of adverse effects can be increased when Etofenamate is combined with Bendazac.
Epirizole The risk or severity of adverse effects can be increased when Epirizole is combined with Bendazac.
Loxoprofen The risk or severity of adverse effects can be increased when Loxoprofen is combined with Bendazac.
Droxicam The risk or severity of adverse effects can be increased when Droxicam is combined with Bendazac.
Tolfenamic acid The risk or severity of adverse effects can be increased when Tolfenamic acid is combined with Bendazac.
Clonixin The risk or severity of adverse effects can be increased when Clonixin is combined with Bendazac.
Tepoxalin The risk or severity of adverse effects can be increased when Tepoxalin is combined with Bendazac.
Flunixin The risk or severity of adverse effects can be increased when Flunixin is combined with Bendazac.
Tinoridine The risk or severity of adverse effects can be increased when Tinoridine is combined with Bendazac.
Alclofenac The risk or severity of adverse effects can be increased when Alclofenac is combined with Bendazac.
Fentiazac The risk or severity of adverse effects can be increased when Fentiazac is combined with Bendazac.
Suxibuzone The risk or severity of adverse effects can be increased when Suxibuzone is combined with Bendazac.
Bumadizone The risk or severity of adverse effects can be increased when Bumadizone is combined with Bendazac.
Alminoprofen The risk or severity of adverse effects can be increased when Alminoprofen is combined with Bendazac.
Bufexamac The risk or severity of adverse effects can be increased when Bufexamac is combined with Bendazac.
Feprazone The risk or severity of adverse effects can be increased when Feprazone is combined with Bendazac.
Difenpiramide The risk or severity of adverse effects can be increased when Difenpiramide is combined with Bendazac.
Nifenazone The risk or severity of adverse effects can be increased when Nifenazone is combined with Bendazac.
Lonazolac The risk or severity of adverse effects can be increased when Lonazolac is combined with Bendazac.
Tenidap The risk or severity of adverse effects can be increased when Tenidap is combined with Bendazac.
Pranoprofen The risk or severity of adverse effects can be increased when Bendazac is combined with Pranoprofen.
Propyphenazone The risk or severity of adverse effects can be increased when Bendazac is combined with Propyphenazone.
Proglumetacin The risk or severity of adverse effects can be increased when Bendazac is combined with Proglumetacin.
Guacetisal The risk or severity of adverse effects can be increased when Bendazac is combined with Guacetisal.
Ethenzamide The risk or severity of adverse effects can be increased when Bendazac is combined with Ethenzamide.
Carbaspirin calcium The risk or severity of adverse effects can be increased when Bendazac is combined with Carbaspirin calcium.
Mofebutazone The risk or severity of adverse effects can be increased when Bendazac is combined with Mofebutazone.
Proquazone The risk or severity of adverse effects can be increased when Bendazac is combined with Proquazone.
Benorilate The risk or severity of adverse effects can be increased when Bendazac is combined with Benorilate.
Pirprofen The risk or severity of adverse effects can be increased when Bendazac is combined with Pirprofen.
Acemetacin The risk or severity of adverse effects can be increased when Bendazac is combined with Acemetacin.
Imidazole salicylate The risk or severity of adverse effects can be increased when Bendazac is combined with Imidazole salicylate.
Benzydamine The risk or severity of adverse effects can be increased when Benzydamine is combined with Bendazac.
Icosapent The risk or severity of adverse effects can be increased when Icosapent is combined with Bendazac.
Antrafenine The risk or severity of adverse effects can be increased when Antrafenine is combined with Bendazac.
Dexibuprofen The risk or severity of adverse effects can be increased when Dexibuprofen is combined with Bendazac.
Trolamine salicylate The risk or severity of adverse effects can be increased when Trolamine salicylate is combined with Bendazac.
Cimicoxib The risk or severity of adverse effects can be increased when Cimicoxib is combined with Bendazac.
Robenacoxib The risk or severity of adverse effects can be increased when Robenacoxib is combined with Bendazac.
Aminophenazone The risk or severity of adverse effects can be increased when Aminophenazone is combined with Bendazac.
Mesalazine The risk or severity of nephrotoxicity can be increased when Mesalazine is combined with Bendazac.
SC-236 The risk or severity of adverse effects can be increased when Bendazac is combined with SC-236.
NS-398 The risk or severity of adverse effects can be increased when Bendazac is combined with NS-398.
Firocoxib The risk or severity of adverse effects can be increased when Firocoxib is combined with Bendazac.
Morniflumate The risk or severity of adverse effects can be increased when Morniflumate is combined with Bendazac.
Talniflumate The risk or severity of adverse effects can be increased when Talniflumate is combined with Bendazac.

Target Protein

Free radicals
Prostaglandin G/H synthase 1 PTGS1
Prostaglandin G/H synthase 2 PTGS2

Referensi & Sumber

Synthesis reference: Bendazac synthesis: BE 699226 (https://worldwide.espacenet.com/publicationDetails/biblio?CC=BE&NR=699226&KC=&FT=E&locale=en_EP), and U.S. Patent US3470194A (https://patents.google.com/patent/US3470194)
Artikel (PubMed)
  • PMID: 3197747
    Rovei V, Escourrou J, Campistron G, Ego D, Thiola A, Ribet A, Houin G: The pharmacokinetics of bendazac-lysine and 5-hydroxybendazac, its main metabolite, in patients with hepatic cirrhosis. Eur J Clin Pharmacol. 1988;35(4):391-6.
  • PMID: 2190795
    Balfour JA, Clissold SP: Bendazac lysine. A review of its pharmacological properties and therapeutic potential in the management of cataracts. Drugs. 1990 Apr;39(4):575-96. doi: 10.2165/00003495-199039040-00007.
  • PMID: 15103205
    Soldo L, Ruggieri A, Milanese C, Pinza M, Guglielmotti A: Bendazac lysine inhibition of human lens epithelial cell adhesion to polymethylmethacrylate intraocular lenses. Ophthalmic Res. 2004 May-Jun;36(3):145-50. doi: 10.1159/000077327.
  • PMID: 7644786
    Prieto de Paula JM, Rodriguez Rodriguez E, Villamandos Nicas V, Sanz de la Fuente H, Prada Minguez A, del Portillo Rubi A: Bendazac hepatotoxicity: analysis of 16 cases. Rev Clin Esp. 1995 Jun;195(6):387-9.
  • PMID: 8658045
    Alcalde M, Garcia-Diaz M, Najarro F, Donoso MS, Cebria L, Pascasio JM: Hepatotoxicity due to lysine salt of bendazac. Scand J Gastroenterol. 1996 Feb;31(2):206-8.
  • PMID: 15990888
    Need AC, Motulsky AG, Goldstein DB: Priorities and standards in pharmacogenetic research. Nat Genet. 2005 Jul;37(7):671-81. doi: 10.1038/ng1593.
  • PMID: 3409993
    Lewis BS, Harding JJ: The major metabolite of bendazac inhibits the glycosylation of soluble lens proteins: a possible mechanism for a delay in cataractogenesis. Exp Eye Res. 1988 Aug;47(2):217-25.
  • PMID: 24464804
    Yu K, Geng X, Chen M, Zhang J, Wang B, Ilic K, Tong W: High daily dose and being a substrate of cytochrome P450 enzymes are two important predictors of drug-induced liver injury. Drug Metab Dispos. 2014 Apr;42(4):744-50. doi: 10.1124/dmd.113.056267. Epub 2014 Jan 24.
Textbook
  • ISBN: 9780857113092
    Alison Brayfield (2017). Martindale the Complete Drug Reference - Volume A (39th ed.). Pharmaceutical Press.

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