Peringatan Keamanan

Reported incidences of agranulocytosis, hyperkalemia, and anaphylaxis. The use of nafamostat has been reported to cause cardiac arrest in patients receiving dialysis due to a sudden change in the patient's condition such as dyspnea. A study suggests that the drug and its metabolites may inhibit the amiloride-sensitive sodium (Na) conductance at the collecting ducts, resulting in an inhibition of K secretion and hyperkalemia A19240. Reported LD50 value from intravenous administration in rats is 16.4mg/kg.

Nafamostat

DB12598

small molecule investigational

Deskripsi

Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.

Struktur Molekul 2D

Berat 347.378
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Approximately 8 minutes [A19227]
Volume Distribusi -
Klirens (Clearance) -

Absorpsi

Data absorpsi tidak tersedia.

Metabolisme

Nafamostat is mainly hydrolyzed by hepatic carboxyesterase and long-chain acyl-CoA hydrolase in human liver cytosol. Main metabolites are p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN) as inactive protease inhibitors.

Rute Eliminasi

Two metabolites of NM, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN), are renally excreted. Nafamostat accumulates in the kidneys.

Interaksi Makanan

1 Data
  • 1. Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Interaksi Obat

719 Data
Apixaban Apixaban may increase the anticoagulant activities of Nafamostat.
Dabigatran etexilate Dabigatran etexilate may increase the anticoagulant activities of Nafamostat.
Dasatinib The risk or severity of bleeding and hemorrhage can be increased when Dasatinib is combined with Nafamostat.
Deferasirox The risk or severity of gastrointestinal bleeding can be increased when Nafamostat is combined with Deferasirox.
Ursodeoxycholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Ursodeoxycholic acid.
Glycochenodeoxycholic Acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Glycochenodeoxycholic Acid.
Cholic Acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Cholic Acid.
Glycocholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Glycocholic acid.
Deoxycholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Deoxycholic acid.
Taurocholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Taurocholic acid.
Obeticholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Obeticholic acid.
Chenodeoxycholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Chenodeoxycholic acid.
Taurochenodeoxycholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Taurochenodeoxycholic acid.
Tauroursodeoxycholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Tauroursodeoxycholic acid.
Bamet-UD2 The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Bamet-UD2.
Dehydrocholic acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Dehydrocholic acid.
Hyodeoxycholic Acid The risk or severity of bleeding and bruising can be increased when Nafamostat is combined with Hyodeoxycholic Acid.
Edoxaban The risk or severity of bleeding can be increased when Edoxaban is combined with Nafamostat.
Ibrutinib The risk or severity of bleeding and hemorrhage can be increased when Ibrutinib is combined with Nafamostat.
Obinutuzumab The risk or severity of bleeding and hemorrhage can be increased when Nafamostat is combined with Obinutuzumab.
Rivaroxaban Nafamostat may increase the anticoagulant activities of Rivaroxaban.
Sugammadex The risk or severity of bleeding and hemorrhage can be increased when Nafamostat is combined with Sugammadex.
Tibolone Tibolone may increase the anticoagulant activities of Nafamostat.
Tipranavir The risk or severity of bleeding and hemorrhage can be increased when Tipranavir is combined with Nafamostat.
Urokinase Urokinase may increase the anticoagulant activities of Nafamostat.
Vitamin E Vitamin E may increase the anticoagulant activities of Nafamostat.
Vorapaxar The risk or severity of bleeding and hemorrhage can be increased when Vorapaxar is combined with Nafamostat.
Bupropion The excretion of Nafamostat can be decreased when combined with Bupropion.
Ginkgo biloba Ginkgo biloba may increase the anticoagulant activities of Nafamostat.
Ifosfamide The risk or severity of bleeding can be increased when Ifosfamide is combined with Nafamostat.
Quinine The therapeutic efficacy of Nafamostat can be increased when used in combination with Quinine.
Quinidine The therapeutic efficacy of Nafamostat can be increased when used in combination with Quinidine.
Tamoxifen The risk or severity of bleeding can be increased when Tamoxifen is combined with Nafamostat.
Toremifene The risk or severity of bleeding can be increased when Toremifene is combined with Nafamostat.
Pentoxifylline The therapeutic efficacy of Nafamostat can be increased when used in combination with Pentoxifylline.
Pentosan polysulfate Pentosan polysulfate may increase the anticoagulant activities of Nafamostat.
Levocarnitine The therapeutic efficacy of Nafamostat can be increased when used in combination with Levocarnitine.
Diethylstilbestrol Diethylstilbestrol may decrease the anticoagulant activities of Nafamostat.
Chlorotrianisene Chlorotrianisene may decrease the anticoagulant activities of Nafamostat.
Conjugated estrogens Conjugated estrogens may decrease the anticoagulant activities of Nafamostat.
Mestranol The risk or severity of adverse effects can be increased when Mestranol is combined with Nafamostat.
Estrone sulfate Estrone sulfate may decrease the anticoagulant activities of Nafamostat.
Quinestrol Quinestrol may decrease the anticoagulant activities of Nafamostat.
Hexestrol Hexestrol may decrease the anticoagulant activities of Nafamostat.
Synthetic Conjugated Estrogens, A Synthetic Conjugated Estrogens, A may decrease the anticoagulant activities of Nafamostat.
Synthetic Conjugated Estrogens, B Synthetic Conjugated Estrogens, B may decrease the anticoagulant activities of Nafamostat.
Polyestradiol phosphate Polyestradiol phosphate may decrease the anticoagulant activities of Nafamostat.
Esterified estrogens Esterified estrogens may decrease the anticoagulant activities of Nafamostat.
Zeranol Zeranol may decrease the anticoagulant activities of Nafamostat.
Equol Equol may decrease the anticoagulant activities of Nafamostat.
Methallenestril Methallenestril may decrease the anticoagulant activities of Nafamostat.
Epimestrol Epimestrol may decrease the anticoagulant activities of Nafamostat.
Moxestrol Moxestrol may decrease the anticoagulant activities of Nafamostat.
Biochanin A Biochanin A may decrease the anticoagulant activities of Nafamostat.
Formononetin Formononetin may decrease the anticoagulant activities of Nafamostat.
Estradiol acetate Estradiol acetate may decrease the anticoagulant activities of Nafamostat.
Estradiol benzoate Estradiol benzoate may decrease the anticoagulant activities of Nafamostat.
Estradiol cypionate Estradiol cypionate may decrease the anticoagulant activities of Nafamostat.
Estradiol valerate Estradiol valerate may decrease the anticoagulant activities of Nafamostat.
Estriol Estriol may decrease the anticoagulant activities of Nafamostat.
Limaprost The risk or severity of adverse effects can be increased when Limaprost is combined with Nafamostat.
Icosapent The risk or severity of bleeding and hemorrhage can be increased when Icosapent is combined with Nafamostat.
Mesalazine The risk or severity of bleeding can be increased when Mesalazine is combined with Nafamostat.
Indomethacin The risk or severity of bleeding and hemorrhage can be increased when Indomethacin is combined with Nafamostat.
Nabumetone The risk or severity of bleeding and hemorrhage can be increased when Nabumetone is combined with Nafamostat.
Ketorolac The risk or severity of bleeding and hemorrhage can be increased when Ketorolac is combined with Nafamostat.
Tenoxicam The risk or severity of bleeding and hemorrhage can be increased when Tenoxicam is combined with Nafamostat.
Celecoxib The risk or severity of bleeding and hemorrhage can be increased when Celecoxib is combined with Nafamostat.
Tolmetin The risk or severity of bleeding and hemorrhage can be increased when Tolmetin is combined with Nafamostat.
Rofecoxib The risk or severity of bleeding and hemorrhage can be increased when Rofecoxib is combined with Nafamostat.
Piroxicam The risk or severity of bleeding and hemorrhage can be increased when Piroxicam is combined with Nafamostat.
Fenoprofen The risk or severity of bleeding and hemorrhage can be increased when Fenoprofen is combined with Nafamostat.
Valdecoxib The risk or severity of bleeding and hemorrhage can be increased when Valdecoxib is combined with Nafamostat.
Diclofenac The risk or severity of bleeding and hemorrhage can be increased when Diclofenac is combined with Nafamostat.
Sulindac The risk or severity of bleeding and hemorrhage can be increased when Sulindac is combined with Nafamostat.
Flurbiprofen The risk or severity of bleeding and hemorrhage can be increased when Flurbiprofen is combined with Nafamostat.
Etodolac The risk or severity of bleeding and hemorrhage can be increased when Etodolac is combined with Nafamostat.
Mefenamic acid The risk or severity of bleeding and hemorrhage can be increased when Mefenamic acid is combined with Nafamostat.
Naproxen The risk or severity of bleeding and hemorrhage can be increased when Naproxen is combined with Nafamostat.
Sulfasalazine The risk or severity of bleeding and hemorrhage can be increased when Sulfasalazine is combined with Nafamostat.
Phenylbutazone The risk or severity of bleeding and hemorrhage can be increased when Phenylbutazone is combined with Nafamostat.
Meloxicam The risk or severity of bleeding and hemorrhage can be increased when Meloxicam is combined with Nafamostat.
Carprofen The risk or severity of bleeding and hemorrhage can be increased when Carprofen is combined with Nafamostat.
Diflunisal The risk or severity of bleeding and hemorrhage can be increased when Diflunisal is combined with Nafamostat.
Salicylic acid The risk or severity of bleeding and hemorrhage can be increased when Salicylic acid is combined with Nafamostat.
Meclofenamic acid The risk or severity of bleeding and hemorrhage can be increased when Meclofenamic acid is combined with Nafamostat.
Oxaprozin The risk or severity of bleeding and hemorrhage can be increased when Oxaprozin is combined with Nafamostat.
Ketoprofen The risk or severity of bleeding and hemorrhage can be increased when Ketoprofen is combined with Nafamostat.
Balsalazide The risk or severity of bleeding and hemorrhage can be increased when Balsalazide is combined with Nafamostat.
Olsalazine The risk or severity of bleeding can be increased when Olsalazine is combined with Nafamostat.
Lumiracoxib The risk or severity of bleeding and hemorrhage can be increased when Lumiracoxib is combined with Nafamostat.
Magnesium salicylate The risk or severity of bleeding and hemorrhage can be increased when Magnesium salicylate is combined with Nafamostat.
Salsalate The risk or severity of bleeding and hemorrhage can be increased when Salsalate is combined with Nafamostat.
Choline magnesium trisalicylate The risk or severity of bleeding and hemorrhage can be increased when Choline magnesium trisalicylate is combined with Nafamostat.
Antrafenine The risk or severity of bleeding and hemorrhage can be increased when Antrafenine is combined with Nafamostat.
Aminophenazone The risk or severity of bleeding and hemorrhage can be increased when Aminophenazone is combined with Nafamostat.
Antipyrine The risk or severity of bleeding and hemorrhage can be increased when Antipyrine is combined with Nafamostat.
Tiaprofenic acid The risk or severity of bleeding and hemorrhage can be increased when Tiaprofenic acid is combined with Nafamostat.
Etoricoxib The risk or severity of bleeding and hemorrhage can be increased when Etoricoxib is combined with Nafamostat.
Taxifolin The risk or severity of bleeding and hemorrhage can be increased when Taxifolin is combined with Nafamostat.

Target Protein

Tumor necrosis factor TNF
Prothrombin F2
Coagulation factor X F10
Coagulation factor XII F12
Serine protease 1 PRSS1
Kallikrein-1 KLK1
Intercellular adhesion molecule 1 ICAM1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 21786254
    Maruyama Y, Yoshida H, Uchino S, Yokoyama K, Yamamoto H, Takinami M, Hosoya T: Nafamostat mesilate as an anticoagulant during continuous veno-venous hemodialysis: a three-year retrospective cohort study. Int J Artif Organs. 2011 Jul;34(7):571-6. doi: 10.5301/IJAO.2011.8535.
  • PMID: 25954127
    Kang MW, Song HJ, Kang SK, Kim Y, Jung SB, Jee S, Moon JY, Suh KS, Lee SD, Jeon BH, Kim CS: Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production. Korean J Physiol Pharmacol. 2015 May;19(3):229-34. doi: 10.4196/kjpp.2015.19.3.229. Epub 2015 Apr 30.
  • PMID: 27610041
    Choi S, Kwon HJ, Song HJ, Choi SW, Nagar H, Piao S, Jung SB, Jeon BH, Kim DW, Kim CS: Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway. Korean J Physiol Pharmacol. 2016 Sep;20(5):539-45. doi: 10.4196/kjpp.2016.20.5.539. Epub 2016 Aug 26.
  • PMID: 26717390
    Choi JY, Kang YJ, Jang HM, Jung HY, Cho JH, Park SH, Kim YL, Kim CD: Nafamostat Mesilate as an Anticoagulant During Continuous Renal Replacement Therapy in Patients With High Bleeding Risk: A Randomized Clinical Trial. Medicine (Baltimore). 2015 Dec;94(52):e2392. doi: 10.1097/MD.0000000000002392.
  • PMID: 24985053
    Chen T, Wang J, Li C, Zhang W, Zhang L, An L, Pang T, Shi X, Liao H: Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition. Sci Rep. 2014 Jul 2;4:5531. doi: 10.1038/srep05531.
  • PMID: 27668164
    Kim HS, Lee KE, Oh JH, Jung CS, Choi D, Kim Y, Jeon JS, Han DC, Noh H: Cardiac arrest caused by nafamostat mesilate. Kidney Res Clin Pract. 2016 Sep;35(3):187-9. doi: 10.1016/j.krcp.2015.10.003. Epub 2015 Nov 12.
  • PMID: 8012693
    Muto S, Imai M, Asano Y: Mechanisms of the hyperkalaemia caused by nafamostat mesilate: effects of its two metabolites on Na+ and K+ transport properties in the rabbit cortical collecting duct. Br J Pharmacol. 1994 Jan;111(1):173-8.

Contoh Produk & Brand

Produk: 0 • International brands: 13
International Brands
  • Berabu — Tobishi Pharmaceutical, Japan
  • Buipel — Teva Seiyaku, Japan
  • Buseron — Sawai Seiyaku, Japan
  • Coahibitor — AY Pharma, Japan
  • Famoset — Towa Yakuhin, Japan
  • Futhan — Torii Yakuhin, Japan
  • Nafaston — Fuji Seiyaku, Japan
  • Nafatat — Nichi-Iko Pharmaceutical, Japan
  • Namostatt — Pola Pharma, Japan
  • Naotamin — Asahi Kasei Pharma, Japan

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