U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C37H48N4O5
Molecular Weight 628.8008
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOPINAVIR

SMILES

CC(C)[C@H](N1CCCNC1=O)C(=O)N[C@H](C[C@H](O)[C@H](CC2=CC=CC=C2)NC(=O)COC3=C(C)C=CC=C3C)CC4=CC=CC=C4

InChI

InChIKey=KJHKTHWMRKYKJE-SUGCFTRWSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021226s030lbl.pdf

Lopinavir (ABT-378) is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir, under the trade names Kaletra.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.3 pM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
KALETRA

Approved Use

KALETRA (lopinavir/ritonavir) is a co-formulation of lopinavir and ritonavir. Lopinavir is an inhibitor of the HIV protease. As co-formulated in KALETRA, ritonavir inhibits the CYP3Amediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir/ KALETRA is indicated in combination with other antiretroviral agents for the treatment of HIV-infection

Launch Date

9.6897597E11
Primary
LOPIMUNE

Approved Use

LOPIMUNE (lopinavir/ritonavir) is a co-formulation of lopinavir and ritonavir. Lopinavir is an inhibitor of the HIV protease. As co-formulated in LOPIMUNE, ritonavir inhibits the CYP3Amediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir/ LOPIMUNEis indicated in combination with other antiretroviral agents for the treatment of HIV-infection
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6539 ng/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9.8 μg/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
11.8 μg/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
60328 ng × h/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
92.6 μg × h/mL
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
154.1 μg × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.4 h
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.5%
400 mg 2 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
LOPINAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
PubMed

PubMed

TitleDatePubMed
Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.
2001 Dec
Lopinavir/ritonavir: a protease inhibitor combination.
2001 Jan 8
DPC 681 and DPC 684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants.
2001 Nov
Serious bradyarrhythmia that was possibly induced by lopinavir-ritonavir in 2 patients with acquired immunodeficiency syndrome.
2002 Aug 15
Gateways to clinical trials.
2002 Dec
Comparison of the efficacy, safety and predictive value of HIV genotyping using distinct ritonavir-boosted protease inhibitors.
2002 Dec
New developments in anti-HIV chemotherapy.
2002 Jul 18
Lopinavir/ritonavir (ABT-378/r).
2002 Mar
Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients.
2002 Mar 1
Delavirdine increases drug exposure of ritonavir-boosted protease inhibitors.
2002 Mar 29
[When nucleoside analogs cannot be tolerated. HIV therapy with booster].
2002 May 9
Delavirdine in rescue regimens.
2002 May-Jun
New anti-HIV agents and targets.
2002 Nov
Pharmacokinetic interaction between lopinavir/r and amprenavir in salvage therapy.
2002 Sep 1
Lopinavir/ritonavir: a review of its use in the management of HIV infection.
2003
Brief report: efficacy and treatment-limiting toxicity with the concurrent use of lopinavir/ritonavir and a third protease inhibitor in treatment-experienced HIV-infected patients.
2003 Apr 15
Effect of therapeutic drug monitoring on outcome in antiretroviral experienced HIV-infected individuals.
2003 Feb
Simultaneous determination of nine antiretroviral compounds in human plasma using liquid chromatography.
2003 Feb 5
Simultaneous quantitative determination of the HIV protease inhibitors indinavir, amprenavir, ritonavir, lopinavir, saquinavir, nelfinavir and the nelfinavir active metabolite M8 in plasma by liquid chromatography.
2003 Jan 15
Determining the relative efficacy of highly active antiretroviral therapy.
2003 Mar 15
Patents

Sample Use Guides

Kaletra (combination of lopinavir and ritonavir) capsules and oral solution should be adminstered orally with food. Dosage for therapy-naïve adult patients KALETRA 400/100 mg (3 capsules or 5.0 mL) twice-daily taken with food or KALETRA 800/200 mg (6 capsules or 10 mL) once-daily taken with food. For therapy-experienced patients KALETRA 400/100 mg (3 capsules or 5.0 mL) twice-daily taken with food.
Route of Administration: Oral
In Vitro Use Guide
MT4 cells and wild-type virus stocks were obtained through the AIDS Research and Reference Reagent Program, AIDS Program, National Institute of Allergy and Infectious Diseases. For drug susceptibility assays, viruses were propagated in CEM cells and titers were determined in MT4 cells. Inhibition of viral replication and compound cytotoxicity were determined in parallel in MT4 cells by a standard colorimetric assay. The EC50s of lopinavir in the absence and presence of 50% human serum were 17 ± 4 and 102 ± 44 nM, respectively.
Name Type Language
LOPINAVIR
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN   INN  
Official Name English
LOPINAVIR, (S-(2S,4S,5S))-
Common Name English
KOLETRA
Common Name English
Lopinavir [WHO-DD]
Common Name English
LOPINAVIR COMPONENT OF KALETRA
Common Name English
(S)-N-((2S,4S,5S)-5-(2-(2,6-DIMETHYLPHENOXY)ACETAMIDO)-4-HYDROXY-1,6-DIPHENYLHEXAN-2-YL)-3-METHYL-2-(2-OXOTETRAHYDROPYRIMIDIN-1(2H)-YL)BUTANAMIDE
Systematic Name English
ALUVIRAN
Common Name English
A-157378.0
Code English
lopinavir [INN]
Common Name English
LOPINAVIR [ORANGE BOOK]
Common Name English
A-157378-0
Code English
LOPINAVIR [USP MONOGRAPH]
Common Name English
LOPINAVIR [WHO-IP]
Common Name English
LOPINAVIR [EMA EPAR]
Common Name English
(1S-(1R*(R*),3R*,4R*))-N-(4-(((2,6-DIMETHYLPHENOXY)ACETYL)AMINO)-3-HYDROXY-5-PHENYL-1-(PHENYLMETHYL)PENTYL)TETRAHYDRO-.ALPHA.-(1-METHYLETHYL)-2-OXO-1(2H)-PYRIMIDINEACETAMIDE
Common Name English
KALETRA COMPONENT LOPINAVIR
Common Name English
LOPINAVIR [MI]
Common Name English
LOPINAVIR [VANDF]
Common Name English
LOPINAVIR [USAN]
Common Name English
ABT-378
Code English
LOPINAVIR [USP-RS]
Common Name English
(αS)-Tetrahydro-N-[(αS)-α-[(2S,3S)-2-hydroxy-4-phenyl-3-[2-(2,6-xylyloxy)acetamido]butyl]phenethyl]-α-isopropyl-2-oxo-1(2H)-pyrimidineacetamide
Common Name English
LOPINAVIR [MART.]
Common Name English
LOPINAVIRUM [WHO-IP LATIN]
Common Name English
LOPINAVIR [EP MONOGRAPH]
Common Name English
LOPINAVIR [JAN]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AE06
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
WHO-ATC J05AR10
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
LIVERTOX NBK547961
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
NDF-RT N0000000246
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
EMA ASSESSMENT REPORTS LOPINAVIR (AUHTORIZED: HIV INFECTIONS)
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
WHO-VATC QJ05AR10
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 6.4.2.3 (LPV/R)
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
EMA ASSESSMENT REPORTS KALETRA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
NDF-RT N0000175889
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
NCI_THESAURUS C97366
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
Code System Code Type Description
SMS_ID
100000089405
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
INN
7798
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
EVMPD
SUB02970MIG
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PRIMARY
DRUG CENTRAL
1601
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
LOPINAVIR
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY Description: A white or almost white powder.Solubility: Freely soluble in methanol and dichloromethane, practically insoluble in water.Category: Antiretroviral (Protease Inhibitor).Storage: Lopinavir should be kept in a tightly closed container, protected from light.Additional information: Lopinavir is hygroscopic and is usually obtained in a hydrated form ; it may exhibit polymorphism.Definition: Lopinavir contains not less than 98.5% and not more than 101.5% of lopinavir (C37H48N4O5), calculated with reference to the anhydrous substance.
NDF-RT
N0000185503
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY P-Glycoprotein Inhibitors [MoA]
HSDB
8138
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
CHEBI
31781
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PRIMARY
DRUG BANK
DB01601
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
RXCUI
195088
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PRIMARY RxNorm
EPA CompTox
DTXSID8046456
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PRIMARY
NDF-RT
N0000190114
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
FDA UNII
2494G1JF75
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
LACTMED
Lopinavir
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
CAS
192725-17-0
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
MERCK INDEX
m6900
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C2095
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PRIMARY
RS_ITEM_NUM
1370101
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PRIMARY
MESH
D061466
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PRIMARY
ChEMBL
CHEMBL729
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PRIMARY
NDF-RT
N0000190107
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
WIKIPEDIA
LOPINAVIR
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
USAN
KK-30
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
DAILYMED
2494G1JF75
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY
PUBCHEM
92727
Created by admin on Fri Dec 15 15:39:15 UTC 2023 , Edited by admin on Fri Dec 15 15:39:15 UTC 2023
PRIMARY