Epristeride

Epristeride
Clinical data
Routes of
administration		 Oral
ATC code None
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 93%[1]
Biological half-life 26 hours[1]
Identifiers
CAS Number 119169-78-7
PubChem (CID) 68741
ChemSpider 10625794
UNII 39517A04PS
ChEMBL CHEMBL290823
Chemical and physical data
Formula C25H37NO3
Molar mass 399.566 g/mol
3D model (Jmol) Interactive image

Epristeride (INN, USAN, BAN, JAN) (brand names Aipuliete, Chuanliu; former developmental code names ONO-9302, SKF-105,657) is a steroidal 5α-reductase inhibitor that has been marketed in China since 2000 for the treatment of benign prostatic hyperplasia (BPH).[2][3][4] It is a selective, transition-state, non-competitive or uncompetitive, irreversible inhibitor of 5α-reductase,[5][6] and is specific to the type II isoform of the enzyme similarly to finasteride and turosteride.[7] Epristeride was under development for the treatment of BPH, androgenic alopecia (pattern hair loss), and acne vulgaris by SmithKline Beecham (now GlaxoSmithKline) in the 1990s and reached phase III clinical trials in the United States, United Kingdom, and Japan,[5] but ultimately was never marketed in these countries and was developed and introduced for the treatment of BPH by Ono Pharmaceutical in China instead.[3]

Epristeride is unique in its mechanism of action 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, and the cofactor NADPH.[7][8] 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.[7][8] However, subsequent clinical data have not supported this hypothesis.[7] 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 dihydrotestosterone (DHT) by only 25 to 54% following 8 days of therapy over a dosage range of 0.4 to 160 mg/day.[7] 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.[7]

References

  1. 1 2 Benincosa LJ, Audet PR, Lundberg D, Zariffa N, Jorkasky DK (April 1996). "Pharmacokinetics and absolute bioavailability of epristeride in healthy male subjects". Biopharmaceutics & Drug Disposition. 17 (3): 249–58. doi:10.1002/(SICI)1099-081X(199604)17:3<249::AID-BDD952>3.0.CO;2-E. PMID 8983399.
  2. ↑ I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 113–. ISBN 978-0-7514-0499-9.
  3. 1 2 http://adisinsight.springer.com/drugs/800002533
  4. ↑ https://www.drugs.com/international/epristeride.html
  5. 1 2 Hedge SS (May 1998). "Epristeride SmithKline Beecham". IDrugs : the Investigational Drugs Journal. 1 (1): 152–7. PMID 18465521.
  6. ↑ Berthaut I, Mestayer C, Portois MC, Cussenot O, Mowszowicz I (August 1997). "Pharmacological molecular evidence for the expression of the two steroid 5 alpha-reductase isozymes in normal and hyperplastic human prostatic cells in culture". The Prostate. 32 (3): 155–63. doi:10.1002/(SICI)1097-0045(19970801)32:3<155::AID-PROS1>3.0.CO;2-K. PMID 9254894.
  7. 1 2 3 4 5 6 Bentham Science Publishers (February 1996). Current Pharmaceutical Design. Bentham Science Publishers. pp. 70–.
  8. 1 2 Rob Bradbury (30 January 2007). Cancer. Springer Science & Business Media. pp. 49–. ISBN 978-3-540-33120-9.


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