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

Details

Stereochemistry ABSOLUTE
Molecular Formula C37H48N4O5
Molecular Weight 628.8022
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOPINAVIR

SMILES

CC(C)[C@@]([H])(C(=N[C@@]([H])(Cc1ccccc1)C[C@@]([H])([C@]([H])(Cc2ccccc2)N=C(COc3c(C)cccc3C)O)O)O)N4CCCN=C4O

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
New drugs.
2001 Jan
Anti-HIV agents. Lopinavir--results after one year.
2001 Winter
Simultaneous quantitative assay of six HIV protease inhibitors, one metabolite, and two non-nucleoside reverse transcriptase inhibitors in human plasma by isocratic reversed-phase liquid chromatography.
2002 Aug
X-ray crystallographic structure of ABT-378 (lopinavir) bound to HIV-1 protease.
2002 Aug
Treatment with lopinavir/ritonavir in heavily pretreated subjects failing multiple antiretroviral regimens in clinical practice.
2002 Aug 15
Serious bradyarrhythmia that was possibly induced by lopinavir-ritonavir in 2 patients with acquired immunodeficiency syndrome.
2002 Aug 15
Limited penetration of lopinavir into seminal plasma of HIV-1-infected men.
2002 Aug 16
Simultaneous determination of indinavir, ritonavir and lopinavir (ABT 378) in human plasma by high-performance liquid chromatography.
2002 Aug 5
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
In vitro antiviral interaction of lopinavir with other protease inhibitors.
2002 Jul
Determination of lopinavir and nevirapine by high-performance liquid chromatography after solid-phase extraction: application for the assessment of their transplacental passage at delivery.
2002 Jul 15
New developments in anti-HIV chemotherapy.
2002 Jul 18
Salvage treatment with lopinavir/ritonavir (Kaletra) in HIV-infected patients failing all current antiretroviral drug families.
2002 Jul-Aug
Kaletra (lopinavir/ritonavir).
2002 Jul-Aug
Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection.
2002 Jun 27
Increasing choices for HIV therapy.
2002 Jun 27
[Plasmatic dosage of antiretroviral drugs by high performance liquid chromathography ].
2002 Mar-Apr
[When nucleoside analogs cannot be tolerated. HIV therapy with booster].
2002 May 9
Delavirdine in rescue regimens.
2002 May-Jun
Encouraging resistance data for Kaletra (lopinavir/ritonavir).
2002 May-Jun
New anti-HIV agents and targets.
2002 Nov
Remission of HIV-associated myelopathy after initiation of lopinavir in a patient with extensive previous exposure to highly active antiretroviral therapy.
2002 Nov 22
Epoxyalcohol route to hydroxyethylene dipeptide isosteres. Stereodivergent synthesis of the diamino alcohol core of ritonavir and its C-2 epimer.
2002 Nov 29
Novel lopinavir analogues incorporating non-Aromatic P-1 side chains--synthesis and structure--activity relationships.
2002 Nov 4
Gateways to clinical trials.
2002 Oct
[Complete auriculoventricular block in a patient treatment with Lopinavir/Ritonavir].
2002 Oct
Clinical use of lopinavir/ritonavir in a salvage therapy setting: pharmacokinetics and pharmacodynamics.
2002 Oct 18
Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir therapy.
2002 Sep
Pharmacokinetic interaction between lopinavir/r and amprenavir in salvage therapy.
2002 Sep 1
Genotypic and phenotypic cross-resistance patterns to lopinavir and amprenavir in protease inhibitor-experienced patients with HIV viremia.
2002 Sep 20
Lopinavir/ritonavir: a review of its use in the management of HIV infection.
2003
The safety and tolerability of switching from a non-failing antiretroviral regimen to lopinavir.
2003 Apr
HIV-1 RNA levels, resistance, and drug diffusion in semen versus blood in patients receiving a lopinavir-containing regimen.
2003 Apr 1
Phase II clinical trials of Kaletra.
2003 Apr 11
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
Determination of protease inhibitors using liquid chromatography-tandem mass spectrometry.
2003 Apr 25
Effect of therapeutic drug monitoring on outcome in antiretroviral experienced HIV-infected individuals.
2003 Feb
Rapid quantification of HIV protease inhibitors in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
2003 Feb
The efficacy of lopinavir in individuals experiencing protease inhibitor failure.
2003 Feb 1
Simultaneous determination of nine antiretroviral compounds in human plasma using liquid chromatography.
2003 Feb 5
Immunovirological outcomes in 70 HIV-1-infected patients who switched to lopinavir/ritonavir after failing at least one protease inhibitor-containing regimen: a retrospective cohort study.
2003 Jan
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
Lopinavir/ritonavir absorption in a gastrectomized patient.
2003 Jan 3
Protease inhibitor shown to hold HIV at undetectable levels.
2003 Jan-Feb
Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.
2003 Mar
Evaluation of antiretroviral drug measurements by an interlaboratory quality control program.
2003 Mar 1
Determining the relative efficacy of highly active antiretroviral therapy.
2003 Mar 15
Small dense LDL and atherogenic lipid profile in HIV-positive adults: influence of lopinavir/ritonavir-containing regimen.
2003 Mar 28
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
LOPINAVIR [WHO-DD]
Common Name English
KOLETRA
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
(.ALPHA.S)-TETRAHYDRO-N-((.ALPHA.S)-.ALPHA.-((2S,3S)-2-HYDROXY-4-PHENYL-3-(2-(2,6-XYLYLOXY)ACETAMIDO)BUTYL)PHENETHYL)-.ALPHA.-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
LOPINAVIR-
Common Name English
Classification Tree Code System Code
WHO-ATC J05AE06
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
WHO-ATC J05AR10
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
LIVERTOX 568
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
NDF-RT N0000000246
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
EMA ASSESSMENT REPORTS LOPINAVIR (AUHTORIZED: HIV INFECTIONS)
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
WHO-VATC QJ05AR10
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.4.2.3 (LPV/R)
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
EMA ASSESSMENT REPORTS KALETRA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
NDF-RT N0000175889
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
NCI_THESAURUS C97366
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
Code System Code Type Description
INN
7798
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
EVMPD
SUB02970MIG
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
DRUG CENTRAL
1601
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
LOPINAVIR
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
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 Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY P-Glycoprotein Inhibitors [MoA]
HSDB
8138
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
DRUG BANK
DB01601
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
RXCUI
195088
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY RxNorm
EPA CompTox
192725-17-0
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
USP_CATALOG
1370101
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY USP-RS
NDF-RT
N0000190114
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
FDA UNII
2494G1JF75
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
LACTMED
Lopinavir
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
CAS
192725-17-0
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
MERCK INDEX
M6900
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C2095
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
MESH
D061466
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL729
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
NDF-RT
N0000190107
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY Organic Anion Transporting Polypeptide 1B1 Inhibitors [MoA]
WIKIPEDIA
LOPINAVIR
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY
PUBCHEM
92727
Created by admin on Fri Jun 25 21:07:49 UTC 2021 , Edited by admin on Fri Jun 25 21:07:49 UTC 2021
PRIMARY