Ritonavir

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Ritonavir
Systematic (IUPAC) name
1,3-thiazol-5-ylmethyl [3-hydroxy-5- [3-methyl-2-[methyl- [(2-propan-2-yl-1,3-thiazol- 4-yl)methyl] carbamoyl] amino-butanoyl] amino-1,6-diphenyl-hexan-2-yl] aminoformate
Identifiers
CAS number	155213-67-5
ATC code	J05AE03
PubChem	392622
DrugBank	APRD00312
Chemical data
Formula	C37H48N6O5S2
Mol. mass	720.946 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	?
Protein binding	98-99%
Metabolism	?
Half life	3-5 hours
Excretion	mostly fecal
Therapeutic considerations
Pregnancy cat.	B (U.S.)
Legal status	℞-only (U.S.)
Routes	?

Ritonavir, with trade name Norvir (Abbott Laboratories), is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS.

Ritonavir is frequently prescribed with HAART, not for its antiviral action, but as it inhibits the same host enzyme that metabolizes other protease inhibitors. This inhibition leads to higher plasma concentrations of these latter drugs, allowing the clinician to lower their dose and frequency and improving their clinical efficacy.

Contents 1 History 2 Method of action 3 Side effects 4 References 5 External links

[edit] History

Ritonavir is manufactured as Norvir by Abbott Laboratories. Research that led to the drug's development was financed by a $3,500,000 federal grant through the National Institutes of Health (NIH) and over $200,000,000 by Abbott Labs. Most of the $200,000,000 figure cited by Abbott paid for clinical trials-despite NIH offering to pay for them-because Abbott was concerned about "public interest" responses to the high prices they projected Norvir would command^[1] The Food and Drug Administration (FDA) approved ritonavir on March 1, 1996, making it the seventh approved antiretroviral drug in the United States. In 2003, Abbott raised the price of a Norvir course from USD $1.71 per day to $8.57 per day, leading to claims of price gouging by patients' groups and some members of Congress. Consumer group Essential Inventions petitioned the NIH to override the Norvir patent, but the NIH announced on August 4, 2004 that it would not invoke its legal right to allow generic production of Norvir, citing potential adverse effects on the pharmaceutical market.^[2]

[edit] Method of action

Ritonavir was originally developed as an inhibitor of HIV protease. It is now rarely used for its own antiviral activity, but remains widely used as a booster of other protease inhibitors. More specifically, ritonavir is used to inhibit a particular liver enzyme that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4). ^[3] The drug's molecular structure inhibits CYP3A4, so a low dose can be used to enhance other protease inhibitors. This discovery, which has drastically reduced the adverse effects and improved the efficacy of PI's and HAART, was first communicated in an article published in the AIDS Journal in 1997 by the University of Liverpool. This effect does come with a price: it also affects the strength of numerous other medications, making it difficult to know how to administer them concurrently. In addition it can cause a large number of side-effects on its own.

[edit] Side effects

One puzzling side effect of ritonavir is hyperglycemia. It appears that it directly inhibits the GLUT4 insulin-regulated transporter, keeping glucose from entering fat and muscle cells. This can lead to insulin resistance and cause problems for Type I diabetics.

[edit] References

• http://www.rxabbott.com/pdf/norpi2a.pdf

[edit] External links

• Norvir (manufacturer's website)
• Ritonavir (patient information)

v • d • e Antivirals used against HIV (HAART) (primarily J05) Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI) Abacavir (ABC)° • Emtricitabine° • Lamivudine (3TC)° • Tenofovir° • Didanosine • Zidovudine (AZT) • Apricitabine† • Stampidine† • Elvucitabine† • Racivir† • Amdoxovir† • Stavudine‡ • Zalcitabine‡ Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) Efavirenz° • Nevirapine • Etravirine • Rilpivirine† • Loviride‡ • Delavirdine‡ Protease Inhibitors (PI) Atazanavir° • Fosamprenavir° • Lopinavir° • Darunavir • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir‡ • Indinavir‡ Entry/fusion inhibitors Enfuvirtide • Maraviroc • Vicriviroc† • PRO 140† • Ibalizumab† Integrase inhibitors Raltegravir • Elvitegravir† Maturation inhibitors Bevirimat† • Vivecon™† Combined formulations Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom Other & experimental agents Foscarnet • Hydroxyurea • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A • Cyanovirin-N • Miltefosine • R-roscovitine† °DHHS preferred first-line agent. †Undergoing clinical trials, not FDA approved. ‡Formerly or rarely used agent.