Epristeride, sold under the brand names Aipuliete and Chuanliu, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

which is used in the treatment of

enlarged prostate Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...

China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Epristeride is a

5α-reductase inhibitor 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...

and works by decreasing the

production Production may refer to: Economics and business * Production (economics) * Production, the act of manufacturing goods * Production, in the outline of industrial organization, the act of making products (goods and services) * Production as a stati ...

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...

(DHT), an

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...

sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects ar ...

, in certain parts of the body like the

prostate gland The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physio ...

. It

inhibit Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s two of the three

form Form is the shape, visual appearance, or configuration of an object. In a wider sense, the form is the way something happens. Form also refers to: *Form (document), a document (printed or electronic) with spaces in which to write or enter data ...

s of

5α-reductase 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...

but is of relatively low

efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...

and can decrease DHT levels in the blood only by about 25 to 54%. Epristeride was under development for the treatment of enlarged prostate,

scalp hair loss Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

, and

acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

and other countries in the 1990s but did not complete development in these countries. Instead, it was developed and introduced for the treatment of enlarged prostate in China in 2000.

Medical uses

Epristeride is used in the treatment of

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...

(BPH), otherwise known as enlarged prostate.

Pharmacology

Pharmacodynamics

Epristeride is a selective, transition-state, non-competitive or uncompetitive, irreversible

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

, and is specific to the type II

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

similarly to

finasteride Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women and as a part of horm ...

and turosteride but unlike

dutasteride Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...

. Epristeride is unique in its

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...

relative to finasteride and dutasteride in that it binds irreversibly to 5α-reductase and results in the formation of an unproductive complex of the 5α-reductase enzyme, the substrate

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

, and the cofactor

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...

. For this reason, testosterone is caught in a trap, and it was initially speculated that the reciprocal increase in intraprostatic levels of testosterone seen with finasteride and dutasteride should not happen with epristeride. However, subsequent clinical data have not supported this hypothesis. Moreover, in spite of the fact that epristeride is a very potent inhibitor of 5α-reductase type II (0.18–2 nM), it has been found to reduce circulating levels of

(DHT) by only 25 to 54% following 8 days of therapy over a dosage range of 0.4 to 160 mg/day. For this reason, relative to other 5α-reductase inhibitors like finasteride and dutasteride, the degree of DHT suppression with epristeride falls short of that desirable for full clinical benefit.

Pharmacokinetics

The

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of epristeride is 93%. It has an

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of 26 hours.

Chemistry

Epristeride, also known as 17β-(''tert''-butylcarbamoyl)androsta-3,5-diene-3-carboxylic acid, is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology ...

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

History

Epristeride was under development for the treatment of BPH,

androgenic alopecia Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front ha ...

(pattern hair loss), and

acne vulgaris Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and po ...

SmithKline Beecham GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

(now

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...

) in the 1990s and reached phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...

, and

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

, but ultimately was never marketed in these countries. Instead, epristeride was developed by Ono Pharmaceutical and introduced for the treatment of BPH in China in 2000.

Society and culture

Generic names

''Epristeride'' is the generic name of the drug and its , , , and .

Brand names

Epristeride is marketed under the brand names Aipuliete and Chuanliu in China.

References

External links

Epristeride - AdisInsight
{{Androgens and antiandrogens 5α-Reductase inhibitors Androstanes Carbamates Carboxylic acids Conjugated dienes Enones Tert-butyl compounds