Lopinavir

Clinical data
Other names	ABT-378
AHFS/Drugs.com	International Drug Names
MedlinePlus	a602015
License data	EU EMA: by INN US DailyMed: Lopinavir
Routes of administration	By mouth
ATC code	J05AR10 (WHO) (with ritonavir)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	Unknown
Protein binding	98-99%
Metabolism	Liver
Elimination half-life	5 to 6 hours
Excretion	Mostly fecal
Identifiers
IUPAC name (2S)-N-2-(2,6-dimethylphenoxy)acetamido-4-hydroxy-1,6-diphenylhexan-2-yl-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
CAS Number	192725-17-0 Y
PubChem CID	92727
DrugBank	DB01601 Y
ChemSpider	83706 Y
UNII	2494G1JF75
KEGG	D01425 Y
ChEMBL	ChEMBL729 Y
CompTox Dashboard (EPA)	DTXSID8046456
ECHA InfoCard	100.281.362
Chemical and physical data
Formula	C37H48N4O5
Molar mass	628.814 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(NC@@H(Cc1ccccc1)C@@H(O)CC@@H(NC(=O)C@@H(N2C(=O)NCCC2)C(C)C)Cc3ccccc3)COc4c(cccc4C)C
InChI InChI=1S/C37H48N4O5/c1-25(2)34(41-20-12-19-38-37(41)45)36(44)39-30(21-28-15-7-5-8-16-28)23-32(42)31(22-29-17-9-6-10-18-29)40-33(43)24-46-35-26(3)13-11-14-27(35)4/h5-11,13-18,25,30-32,34,42H,12,19-24H2,1-4H3,(H,38,45)(H,39,44)(H,40,43)/t30-,31-,32-,34-/m0/s1 Y Key:KJHKTHWMRKYKJE-SUGCFTRWSA-N Y
(verify)

Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir).^[1]

It was patented in 1995 and approved for medical use in 2000.^[2] Considered now as second-line therapy in the West, it is still prescribed in LMIC, especially among children living with HIV. Lopinavir and ritonavir can be taken as a tablet or an oral solution, a preferred option in children. In the early stages of COVID-19 pandemics, lopinavir was repurposed against the SARS-CoV-2 virus in the hope of disturbing its protease activity.^[3]

Side effectsedit

Side effects, interactions, and contraindications have only been evaluated in the drug combination lopinavir/ritonavir. They include nausea, vomiting, and stomach aches.^{[citation needed]}

Pharmacologyedit

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

Reports are contradictory regarding lopinavir penetration into the cerebrospinal fluid (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]

Researchedit

A 2014 study indicates that lopinavir is effective against the human papilloma virus (HPV). The study used the equivalent of one tablet twice a day applied topically to the cervices of women with high-grade and low-grade precancerous conditions. After three months of treatment, 82.6% of the women who had high-grade disease had normal cervical conditions, confirmed by smears and biopsies.^[6] Lopinavir has been shown to impair protein synthesis via AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K) activation, a mechanism that is similar to the antiviral effect of protein phosphatase 1 inhibitors.^[7][8]

Lopinavir was found to inhibit MERS-CoV replication in the low-micromolar range in cell cultures.^[9] In 2020, lopinavir/ritonavir was found not to work in severe COVID-19. In this trial the medication was started typically around 13 days after the start of symptoms.^[10]

A long-acting injectable formulation of lopinavir is under clinical trial aiming at monthly dosing (NCT05850728).

Referencesedit

External linksedit

• "Lopinavir". Drug Information Portal. U.S. National Library of Medicine.