Lopinavir
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| Image:Lopinavir.svg | |
| Lopinavir
| |
| Systematic (IUPAC) name | |
| (2S)-N-[(2S,4S,5S)-5-{[2-(2,6-dimethylphenoxy) acetyl]amino}-4-hydroxy-1,6-diphenyl-hexan-2-yl]- 3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide | |
| Identifiers | |
| CAS number | |
| ATC code | J05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C37H48N4O5 |
| Mol. mass | 628.810 g/mol |
| Pharmacokinetic data | |
| Bioavailability | Unknown |
| Protein binding | 98-99% |
| Metabolism | Hepatic |
| Half life | 5 to 6 hours |
| Excretion | Mostly fecal |
| Therapeutic considerations | |
| Pregnancy cat. |
C (U.S.) |
| Legal status | |
| Routes | Oral |
Lopinavir (ABT-378) is an antiretroviral of the protease inhibitor class. It is marketed by Abbott as Kaletra®, a co-formulation with a sub-therapeutic dose of ritonavir, as a component of combination therapy to treat HIV/AIDS.
As of 2006, lopinavir/ritonavir forms part of the preferred combination for first-line therapy recommended by the US DHHS.[1] It is available as capsules, tablets and oral solution.
Contents |
History
Lopinavir was developed by Abbott in an attempt to improve on the HIV resistance and serum protein-binding properties of the company's earlier protease inhibitor, ritonavir.[1] Administered alone, lopinavir has insufficient bioavailability; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of cytochrome P450 3A4.[1] Abbott therefore pursued a strategy of co-administering lopinavir with sub-therapeutic doses of ritonavir, and lopinavir is only marketed as a co-formulation with ritonavir. It is the first multi-drug capsule to contain a drug not available individually.
Lopinavir/ritonavir was approved by the US FDA on 15 September 2000, and in Europe in April 2001. Its patent will expire in the US on June 26, 2016.
Pharmacology
Lopinavir is highly bound to plasma proteins (98-99%).[1]
There are contradictory reports regarding lopinavir penetration into the CSF. Anecdotal reports state that lopinavir cannot be detected in the CSF; however, a study of paired CSF-plasma samples from 26 patients receiving lopinavir/ritonavir found lopinavir CSF levels above the IC50 in 77% of samples.[1]
Adverse effects
The most common adverse effects observed with lopinavir/ritonavir are diarrhea and nausea. In key clinical trials, moderate or severe diarrhea occurred in up to 27% of patients, and moderate/severe nausea in up to 16%.[1] Other common adverse effects include abdominal pain, asthenia, headache, vomiting and, particularly in children, rash.[1]
Raised liver enzymes and hyperlipidemia (both hypertriglyceridemia and hypercholesterolemia) are also commonly observed during lopinavir/ritonavir treatment.
Access
As a result of high prices and the spread of HIV infection, the government of Thailand issued a compulsory license on 29 January 2007 to produce and/or import generic lopinavir/ritonavir.[1] In response, Abbott Laboratories pulled registration for lopinavir and seven of their other new drugs in Thailand, citing the Thai government's lack of respect for patents.[1] Abbott's attitude has been denounced by several NGOs worldwide, including a netstrike initiated by Act Up-Paris and a public call to boycott all of Abbott's medicines by the French NGO AIDES.[1]
References
External link
Antivirals, other than for HIV (primarily J05, also S01AD and D06BB) | |
|---|---|
| Anti-herpesvirus (DNA, I) | guanine analogues (Aciclovir, Famciclovir, Ganciclovir, Penciclovir, Valaciclovir, Valganciclovir) • nucleoside analogues (Idoxuridine, Trifluridine, Vidarabine) • Cidofovir • Docosanol • Fomivirsen • Foscarnet • Tromantadine |
| HPV/MC (DNA, I) | Imiquimod • Podophyllotoxin |
| Hepatitis B (DNA, VII) | Adefovir • Interferon alfa-2b • Pegylated interferon alfa-2a • Entecavir • Lamivudine • Telbivudine • Tenofovir† |
| Hepatitis C (RNA, IV) | Pegylated interferon alpha • Ribavirin • Taribavirin† • Boceprevir† |
| Picornavirus (RNA, IV) | Pleconaril† |
| Anti-influenza agents (RNA, V) | Arbidol
adamantane derivatives/M2 inhibitors (Amantadine, Rimantadine) neuraminidase inhibitors (Oseltamivir, Zanamivir, Peramivir†) |
| HIV (Reverse, VI) | See HIV pharm |
| Other antiviral agents | general (Inosine, Interferon) |
| †Undergoing clinical trials, not FDA approved. | |
Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
