Lopinavir

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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	192725-17-0
ATC code	J05AE06
PubChem	92727
DrugBank	EXPT00388
Chemical data
Formula	C37H48N4O5
Mol. mass	628.810 g/mol
SMILES	eMolecules & PubChem
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	℞-only (U.S.), POM (UK)
Routes	Oral

Lopinavir (ABT-378) is an antiretroviral of the protease inhibitor class. It is marketed by Abbott as Kaletra (capsules) and Aluvia (non-refrigerated tablets), 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.^[1]

As of 2006, lopinavir/ritonavir forms part of the preferred combination for first-line therapy recommended by the US DHHS.^[2] It is available as capsules, tablets and oral solution.

Contents 1 History 2 Pharmacology 3 Adverse effects 4 Access 5 References 6 External links

[edit] 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.^[3] 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.^[3] 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.

[edit] Pharmacology

Lopinavir is highly bound to plasma proteins (98-99%).^[4]

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.^[5]

[edit] 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%.^[4] Other common adverse effects include abdominal pain, asthenia, headache, vomiting and, particularly in children, rash.^[4]

Raised liver enzymes and hyperlipidemia (both hypertriglyceridemia and hypercholesterolemia) are also commonly observed during lopinavir/ritonavir treatment.

[edit] 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.^[6] 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.^[7] 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.^[8]

[edit] References

[edit] External links

• Abbott: Kaletra (lopinavir/ritonavir) tablets

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