Camostat is a

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Seri ...

inhibitor. Serine protease enzymes have a variety of functions in the body, and so camostat has a diverse range of uses. Camostat is approved in Japan for the treatment of chronic

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...

and postoperative

reflux esophagitis Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...

.http://www.shijiebiaopin.net/upload/product/201272318373223.PDF The oral proteolytic enzyme inhibitor has been on the market since 1985 under the trade name Foipan Tablets. The manufacturer is

Ono Pharmaceutical is one of the largest pharmaceutical companies in Japan. It is headquartered in Chuo-ku, Osaka, Japan, with its major plants in Higashinari-ku, Osaka, and Fujinomiya, Shizuoka., and its central research institute at Minase, Shimamoto-cho, Mi ...

. The drug is used in the treatment of some forms of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

and is also effective against some viral infections, as well as inhibiting

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

in liver or kidney disease or pancreatitis.

Pharmacology

It is an inhibitor of the enzyme transmembrane protease, serine 2 (TMPRSS2). For chronic

camostat's typical dose is 600 mg daily, for postoperative

300 mg are taken. The daily dose is split in 3 doses and taken after each meal.

Side effects

As side effects allergic reactions including

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the foll ...

, hypersensitivity,

hyperkalemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

, platelet and leukocyte depletion, liver dysfunction, jaundice have been reported.

COVID-19

Inhibition of TMPRSS2 partially blocked infection by

SARS-CoV Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for ...

and

Human coronavirus NL63 Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, an ...

HeLa HeLa (; also Hela or hela) is an immortalized cell line used in scientific research. It is the oldest and most commonly used human cell line. The line is derived from cervical cancer cells taken on February 8, 1951, named after Henrietta ...

cell cultures. Another ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

'' study showed that camostat significantly reduces the infection of Calu-3 lung cells by

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...

, the virus responsible for

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly ...

. It is currently in many Phase 1 and Phase 2 clinical trials. Camostat decreased CRP levels better compared to

Lopinavir Lopinavir is an anti retroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir). It was patented in 1995 and approved for medical ...

Ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor ...

in a small study of mild COVID-19 patients. Camostat decreased COVID-19 severity, improved inflammatory markers and oxygenation compared to

hydroxychloroquine Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, an ...

treated patients. A study of 205 COVID-19 patients treated with Camostat, carried out at Aarhus University Hospital in

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and concluding in April 2021, showed no noticeable effects of Camostat on duration of hospitalisation or severity of the cases, but noted that higher doses (the study used 600 mg Camostat daily dosage) might still have a possible effect. On July 1, 2021, the AIDS Clinical Trials Group announced that the Camostat group on the "ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies Trial" would not be moving forward to Phase 3. The trial demonstrated no safety concerns but also no changes in viral shedding or symptom improvement.

References

External links

* * {{Portal bar , Medicine Acetamides 4-Aminobenzoate esters Guanidines Phenol esters Serine protease inhibitors Dimethylamino compounds COVID-19 drug development