Nelfinavir

Nelfinavir

File:Nelfinavir.svg
Systematic (IUPAC) name
(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
Pharmacokinetic data
Bioavailability	Uncertain; improved by taking with food
Protein binding	>98%
Metabolism	Hepatic metabolism by CYP450 incl. CYP3A4
Biological half-life	3.5 - 5 hours
Excretion	Metabolites eliminated in faeces
Identifiers
CAS Number	159989-64-7
ATC code	J05AE04 (WHO)
PubChem	CID 64143
DrugBank	APRD00003
Chemical data
Formula	C32H45N3O4S
Molar mass	567.784 g/mol[[]]
Physical data
Melting point	349.94 °C (661.89 °F)
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Nelfinavir (Viracept) is an antiretroviral drug used in the treatment of the human immunodeficiency virus (HIV). Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is generally used in combination with other antiretroviral drugs.

Nelfinavir mesylate (Viracept, formally AG1343) is a potent and orally bioavailable human immunodeficiency virus HIV-1 protease inhibitor (Ki=2nM) and is being widely prescribed in combination with HIV reverse transcriptase inhibitors for the treatment of HIV infection.

History

Nelfinavir was developed by Agouron Pharmaceuticals as part of a joint venture with Japan Tobacco. Agouron Pharmaceuticals was acquired by Warner Lambert in 1999 and is now a subsidiary of Pfizer. It is marketed in Europe by Hoffman-La Roche. The Food and Drug Administration approved it for therapeutic use on March 14, 1997, making it the twelfth approved antiretroviral. The initial product launched proved to be the largest "biotech launch" in the history of the pharmaceutical industry achieving first full year sales exceeding $335M US. Agouron's patent on the drug will expire in 2014.

On the 6th June 2007 both the Medicines and Healthcare products Regulatory Agency and the European Medicines Agency put out an alert requesting the recall of any of the drug in circulation because of fears that batches of the therapy may have been contaminated with potentially cancer-causing chemicals

Pharmacology

Nelfinavir should be taken with food. The bioavailability of Nelfinavir is increased 2.5 to 5 times when taken with food. Taking the drug with food also decreases the risk of diarrhea as a side effect.

Mode of action

Nelfinavir is a protease inhibitor: it inhibits HIV-1 and HIV-2 proteases. This protease is an enzyme which cleaves viral protein molecules into smaller fragments, and it is vital for both the replication of the virus within the cell and also the release of mature viral particles from an infected cell. Though this mode of action is common to all protease inhibitors, the precise mode of binding of nelfinavir to the enzyme may be sufficiently unique to reduce cross-resistance between it and other PIs. Also, not all PIs inhibit both HIV-1 and HIV-2 proteases.

Toxicity

Nelfinavir can produce a range of adverse effects. Common (experienced by more than one in one hundred patients; greater than 1%) are flatulence, diarrhea or abdominal pain. Infrequent (experienced by one in one thousand to one in one hundred patients; 0.01 - 0.1%) adverse effects are fatigue, urination, rash, mouth ulcers or hepatitis. Rarely (less than one in one thousand patients; under 0.01%) nephrolithiasis, arthralgia, Leukopenia, pancreatitis or allergic reactions may occur.

Potential anti-cancer activity

Nelfinavir is currently under investigation for potential use as an anti-cancer agent. When applied to cancer cells in culture (in vitro), it is able to inhibit the growth of a variety of different cancer types and triggers cell death (apoptosis). When Nelfinavir was given to laboratory mice with tumors of the prostate or of the brain, it could suppress tumor growth in these animals. Although these laboratory outcomes are promising, it has not yet convincingly been established whether such tumor therapeutic effects can also be achieved in human cancer patients.

In the United States, there are several clinical trials currently going on that seek to verify whether nelfinavir is effective as a cancer therapeutic agent in humans. In some of these trials, nelfinavir is used alone in monotherapy fashion, whereas in others it is combined with other modes of cancer therapy, such as well-established chemotherapeutic agents or radiation therapy. It might take several years for most of these studies to be completed and their results published.

Interactions

Nelfinavir's interaction profile is similar to that of other protease inhibitors. Most interactions occur at the level of the Cytochrome P450 isozymes 3A4 and CYP2C19, by which nelfinavir is metabolised.

See also

• HIV-1 protease
• Cremophor EL
• Castor oil

References

• Actual photo of Nelfinavir and further Nelfinavir information

de:Nelfinavir