LOPINAVIR

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 Search

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

Molecular Formula	C37H48N4O5
Molecular Weight	628.8008
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9835517
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9835517	Inhibitor 8297		1.3 pM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV infection 21 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021226s030lbl.pdf	Primary		Approved 8429	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 2000
HPV positive with high grade squamous intraepithelial lesions 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26824902	Primary		Phase II 1132	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

C_max

Value	Dose	Co-administered	Analyte	Population
6539 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24632753	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.8 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021251s052_021906s046lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
11.8 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021251s052_021906s046lbl.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
60328 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24632753	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
92.6 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021251s052_021906s046lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
154.1 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021251s052_021906s046lbl.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24632753	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021251s052_021906s046lbl.pdf	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	LOPINAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31781	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31781
MolPort	MolPort-003-848-410	https://www.molport.com/shop/molecule-link/MolPort-003-848-410
Selleck Chemicals	Lopinavir	http://www.selleckchem.com/products/Lopinavir.html
ZINC	ZINC000003951740	http://zinc15.docking.org/substances/ZINC000003951740
eMolecules	6719306	https://www.emolecules.com/cgi-bin/more?vid=6719306

PubMed

Title	Date	PubMed
New drugs.	2001 Jan	12184254
New drug approvals in 2000.	2001 Jul-Aug	12016673
Anti-HIV agents. Lopinavir--results after one year.	2001 Winter	12132436
Simultaneous determination of the six HIV protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) plus M8 nelfinavir metabolite and the nonnucleoside reverse transcription inhibitor efavirenz in human plasma by solid-phase extraction and column liquid chromatography.	2002 Apr	11897976
[After 3 years no resistance development. Protease inhibitor with staying power].	2002 Apr 9	12043076
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	12142642
X-ray crystallographic structure of ABT-378 (lopinavir) bound to HIV-1 protease.	2002 Aug	12057670
Simultaneous determination of indinavir, ritonavir and lopinavir (ABT 378) in human plasma by high-performance liquid chromatography.	2002 Aug 5	12113989
Gateways to clinical trials.	2002 Dec	12616965
Comparison of the efficacy, safety and predictive value of HIV genotyping using distinct ritonavir-boosted protease inhibitors.	2002 Dec	12458138
In vitro antiviral interaction of lopinavir with other protease inhibitors.	2002 Jul	12069982
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	12076682
New developments in anti-HIV chemotherapy.	2002 Jul 18	12084468
Salvage treatment with lopinavir/ritonavir (Kaletra) in HIV-infected patients failing all current antiretroviral drug families.	2002 Jul-Aug	12187504
Kaletra (lopinavir/ritonavir).	2002 Jul-Aug	12086554
High-performance liquid chromatographic method for the simultaneous determination of the six HIV-protease inhibitors and two non-nucleoside reverse transcriptase inhibitors in human plasma.	2002 Jun	12021635
Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection.	2002 Jun 27	12087139
Increasing choices for HIV therapy.	2002 Jun 27	12087136
Efavirenz-induced skin eruption and successful desensitization.	2002 Mar	11895054
[Plasmatic dosage of antiretroviral drugs by high performance liquid chromathography ].	2002 Mar-Apr	12185966
[When nucleoside analogs cannot be tolerated. HIV therapy with booster].	2002 May 9	12116561
Delavirdine in rescue regimens.	2002 May-Jun	12064317
Encouraging resistance data for Kaletra (lopinavir/ritonavir).	2002 May-Jun	12064017
Remission of HIV-associated myelopathy after initiation of lopinavir in a patient with extensive previous exposure to highly active antiretroviral therapy.	2002 Nov 22	12441823
Epoxyalcohol route to hydroxyethylene dipeptide isosteres. Stereodivergent synthesis of the diamino alcohol core of ritonavir and its C-2 epimer.	2002 Nov 29	12444650
Novel lopinavir analogues incorporating non-Aromatic P-1 side chains--synthesis and structure--activity relationships.	2002 Nov 4	12372511
Gateways to clinical trials.	2002 Oct	12500432
[Complete auriculoventricular block in a patient treatment with Lopinavir/Ritonavir].	2002 Oct	12372245
Clinical use of lopinavir/ritonavir in a salvage therapy setting: pharmacokinetics and pharmacodynamics.	2002 Oct 18	12370509
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	12487383
Pharmacokinetic interaction between lopinavir/r and amprenavir in salvage therapy.	2002 Sep 1	12352158
Genotypic and phenotypic cross-resistance patterns to lopinavir and amprenavir in protease inhibitor-experienced patients with HIV viremia.	2002 Sep 20	12396453
Lopinavir/ritonavir: a review of its use in the management of HIV infection.	2003	12662125
The safety and tolerability of switching from a non-failing antiretroviral regimen to lopinavir.	2003 Apr	12643876
HIV-1 RNA levels, resistance, and drug diffusion in semen versus blood in patients receiving a lopinavir-containing regimen.	2003 Apr 1	12640207
Phase II clinical trials of Kaletra.	2003 Apr 11	12660556
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	12679700
Determination of protease inhibitors using liquid chromatography-tandem mass spectrometry.	2003 Apr 25	12650761
Effect of therapeutic drug monitoring on outcome in antiretroviral experienced HIV-infected individuals.	2003 Feb	12600653
Rapid quantification of HIV protease inhibitors in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.	2003 Feb	12577282
The efficacy of lopinavir in individuals experiencing protease inhibitor failure.	2003 Feb 1	12571536
Simultaneous determination of nine antiretroviral compounds in human plasma using liquid chromatography.	2003 Feb 5	12505781
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	12493805
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	12482492
Lopinavir/ritonavir absorption in a gastrectomized patient.	2003 Jan 3	12478084
Protease inhibitor shown to hold HIV at undetectable levels.	2003 Jan-Feb	12585228
Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children.	2003 Mar	12634581
Evaluation of antiretroviral drug measurements by an interlaboratory quality control program.	2003 Mar 1	12626888
Determining the relative efficacy of highly active antiretroviral therapy.	2003 Mar 15	12660935
Small dense LDL and atherogenic lipid profile in HIV-positive adults: influence of lopinavir/ritonavir-containing regimen.	2003 Mar 28	12646808

Patents

Sample Use Guides

In Vivo Use Guide

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:39:15 GMT 2023` Edited by `admin` on `Fri Dec 15 15:39:15 GMT 2023`
Record UNII	2494G1JF75
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LOPINAVIR

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