Lopinavir 192725-17-0
Lopinavir (ABT-378) is an antiretroviral of the protease inhibitor class. It is marketed by Abbott as Kaletra (high-income countries) and Aluvia (low-income countries), both of which represent a co-formulation with a sub-therapeutic dose of ritonavir, as a component of combination therapy to treat HIV/AIDS. The Kaletra formulation has also been used successfully as monotherapy in some studies. As of 2006, lopinavir/ritonavir forms part of the preferred combination for first-line therapy recommended by the US DHHS. It is available as capsules, tablets and oral solution.
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. 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.
Pharmacology
Lopinavir is highly bound to plasma proteins (98-99%). 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.
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%. .
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 versions of lopinavir and ritonavir. 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.
| Systematic (IUPAC) name: | (2S)-N-[(2S,4S,5S)-5-[2-(2,6-dimethylphenoxy)acetamido]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide |
|---|---|
| Lopinavir CAS number: | 192725-17-0 |
| ATC code: | J05AE06 |
| PubChem: | 92727 |
| DrugBank: | EXPT00388 |
| Formula: | C37 H48 N4 O5 |
| Molecular mass: | 628.810 [[Gram g/mol |
| Lopinavir Assay/Purity: | Typically NLT 98% |
