Lopinavir

Lopinavir

File:Lopinavir.svg
Clinical data
Pregnancy category	C (U.S.)
Routes of administration	Oral
ATC code	J05AE06 (WHO)
Legal status
Legal status	℞-only (U.S.), POM (UK)
Pharmacokinetic data
Bioavailability	Unknown
Protein binding	98-99%
Metabolism	Hepatic
Elimination half-life	5 to 6 hours
Excretion	Mostly fecal
Identifiers
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
CAS Number	192725-17-0
PubChem CID	92727
DrugBank	EXPT00388
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C37H48N4O5
Molar mass	628.810 g/mol

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. 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. 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%).

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%. Other common adverse effects include abdominal pain, asthenia, headache, vomiting and, particularly in children, rash.

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. 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. 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.

External link

• Abbott: Kaletra (lopinavir/ritonavir) tablets