Article: Lopinavir

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	J05AE06
PubChem	92727
DrugBank	EXPT00388
Chemical data
Formula	C37H48N4O5
Mol. weight	628.810 g/mol
Pharmacokinetic data
Bioavailability	Unknown
Protein binding	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®, 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.

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.^[2] 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.^[2] 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.

Lopinavir/ritonavir was approved by the US FDA on 15 September 2000, and in Europe in April 2001.

Pharmacology

Lopinavir is highly bound to plasma proteins (98%).

There are contradictory reports regarding lopinavir concentrations in CSF. Anecdotal reports state that there is no detectable lopinavir in CSF, but a systematic study of CSF-plasma pairs found useful levels of lopinavir in 26 patients.^[3]

Adverse effects

The most common adverse effects observed with lopinavir/ritonavir are diarrhoea and nausea. In key clinical trials, moderate or severe diarrhoea 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.