Identification

Name
Lopinavir
Accession Number
DB01601  (EXPT00388)
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
  • LPV
External IDs
A-157378-0 / A-157378.0 / ABT-378
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
KaletraLopinavir (133.3 mg) + Ritonavir (33.3 mg)CapsuleOralAbbvie2001-03-092012-11-02Canada
KaletraLopinavir (80 mg) + Ritonavir (20 mg)SolutionOralAbbvie2001-03-09Not applicableCanada
KaletraLopinavir (100 mg/1) + Ritonavir (25 mg/1)Tablet, film coatedOralAbbvie2010-06-18Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralRemedy Repack2008-09-052017-01-16Us
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralDispensing Solutions, Inc.2010-06-18Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralPd Rx Pharmaceuticals, Inc.2010-06-18Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-04-11Not applicableUs
KaletraLopinavir (100 mg) + Ritonavir (25 mg)TabletOralAbbvie2008-08-11Not applicableCanada
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralAbbvie2010-06-18Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralA-S Medication Solutions2010-06-18Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)TabletOralRemedy Repack2010-09-272013-05-16Us
International/Other Brands
Aluviran / Koletra
Categories
UNII
2494G1JF75
CAS number
192725-17-0
Weight
Average: 628.8008
Monoisotopic: 628.362470666
Chemical Formula
C37H48N4O5
InChI Key
KJHKTHWMRKYKJE-SUGCFTRWSA-N
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
IUPAC Name
(2S)-N-[(2S,4S,5S)-5-[2-(2,6-dimethylphenoxy)acetamido]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
SMILES
CC(C)[C@H](N1CCCNC1=O)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)COC1=C(C)C=CC=C1C)CC1=CC=CC=C1

Pharmacology

Indication

Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.

Associated Conditions
Pharmacodynamics

Lopinavir is an antiretroviral of the protease inhibitor class. Inhibiting HIV-1 protease (responsible for protein cleavage), results in selectively inhibiting the cleavage of HIV gag and gag-pol polyproteins, thereby preventing viral maturation.

Mechanism of action

Lopinavir inhibits the HIV viral protease enzyme. This prevents cleavage of the gag-pol polyprotein and, therefore, improper viral assembly results. This subsequently results in non-infectious, immature viral particles.

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
Absorption

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.

Volume of distribution
Not Available
Protein binding

Lopinavir is highly bound to plasma proteins (98-99%).

Metabolism

Hepatic. Lopinavir is extensively metabolized by the hepatic cytochrome P450 system, almost exclusively by the CYP3A isozyme.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Although human experience of acute overdosage with lopinavir is limited, accidental ingestion of the product by a young child could result in significant alcohol-related toxicity and could approach the potential lethal dose of alcohol.

Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Lopinavir can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Lopinavir can be decreased when combined with (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Lopinavir.
3,5-diiodothyropropionic acidThe metabolism of Lopinavir can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lopinavir.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Lopinavir.
5-androstenedioneThe metabolism of Lopinavir can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Lopinavir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Lopinavir can be decreased when combined with 6-O-benzylguanine.
AbacavirLopinavir may decrease the excretion rate of Abacavir which could result in a higher serum level.
Food Interactions
  • Avoid St.John's Wort.
  • Take with food.

References

Synthesis Reference
US5914332
General References
Not Available
External Links
Human Metabolome Database
HMDB0015539
KEGG Drug
D01425
KEGG Compound
C12871
PubChem Compound
92727
PubChem Substance
46508588
ChemSpider
83706
BindingDB
578
ChEBI
31781
ChEMBL
CHEMBL729
Therapeutic Targets Database
DAP000708
PharmGKB
PA450264
HET
AB1
RxList
RxList Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Lopinavir
ATC Codes
J05AR10 — Lopinavir and ritonavir
PDB Entries
1mui / 1rv7 / 2o4s / 2q5k / 2qhc / 2rkf / 2rkg / 2z54 / 3ogq / 4l1a
show 2 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedOtherHealthy Volunteers1
0CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Isavuconazole / Pharmacokinetics of Lopinavir/Ritonavir1
1CompletedNot AvailableHepatitis C Viral Infection1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedOtherDrug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics1
1CompletedOtherFenofibrate / Glucuronosyltransferase / Human Immunodeficiency Virus (HIV) / Hypertriglyceridemias / Protease Inhibitors1
1CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS)1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHepatitis C Viral Infection / Thrombocytopenias1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections5
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Pregnancy1
1CompletedTreatmentInsulin Resistance1
1CompletedTreatmentTuberculosis Infection1
1SuspendedTreatmentHuman Immunodeficiency Virus (HIV)1
1TerminatedTreatmentHuman Immunodeficiency Virus (HIV) / Tuberculosis Infection1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
1, 2CompletedTreatmentInfection, Human Immunodeficiency Virus I / Pf Subclinical Parasitemia1
1, 2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
2CompletedTreatmentFibrosis, Liver / Hepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections20
2RecruitingOtherHuman Immunodeficiency Virus (HIV) / Tuberculosis Infection1
2TerminatedTreatmentAnaplastic Astrocytoma (AA) / Anaplastic Ependymoma / Anaplastic Oligodendroglioma (AO) / Brain Stem Gliomas / Giant Cell Glioblastoma / Glioblastomas / Gliosarcoma / Mixed Gliomas / Neoplasms, Brain1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
2Unknown StatusPreventionHuman Immunodeficiency Virus (HIV) / Viral Hepatitis B1
2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2WithdrawnTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentAcute HIV Infection1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
2, 3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Pediatric AIDS1
2, 3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Pregnancy1
3Active Not RecruitingTreatmentAcute HIV Infection1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
3CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections4
3CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHIV-Infected Children1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections23
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentInfection, Human Immunodeficiency Virus I2
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
3TerminatedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3Unknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3Unknown StatusTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) Infections2
3Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3WithdrawnTreatmentHuman Immunodeficiency Virus (HIV)1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) / Proteinuria1
4CompletedBasic ScienceCardiovascular Disease (CVD) / Dyslipidemias / Glucose Metabolism Disorders / Human Immunodeficiency Virus (HIV) Infections / Lipodystrophies / Metabolic Diseases1
4CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1
4CompletedDiagnosticAIDS-Related Opportunistic Infections / Human Immunodeficiency Virus (HIV) Infections1
4CompletedPreventionHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections3
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Tuberculosis Infection1
4CompletedTreatmentHIV test positive / Malnourished1
4CompletedTreatmentHIV/AIDS Treatment / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHepatitis C Infection With HIV Co-Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)8
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections12
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipoatrophy1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Mitochondrial Toxicity1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Tuberculosis Infection1
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)2
4RecruitingPreventionHIV/AIDS and Infections1
4RecruitingTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Tuberculosis Infection1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4TerminatedNot AvailableHuman Immunodeficiency Virus (HIV) Infections2
4TerminatedTreatmentAcquired Immune Deficiency Syndrome (AIDS)1
4TerminatedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections8
4Unknown StatusPreventionHIV-Associated Lipodystrophy Syndrome / Human Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS)1
4Unknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections4
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV)3
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections6
Not AvailableCompletedNot AvailableInfection, Human Immunodeficiency Virus I3
Not AvailableCompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedOtherEndothelial Dysfunction1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV)1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections12
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies / Wasting Disease1
Not AvailableCompletedTreatmentPrimary Biliary Cholangitis1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
Not AvailableTerminatedTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableTerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusTreatmentAIDS/HIV problem1
Not AvailableUnknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV)1
Not AvailableWithdrawnTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableWithdrawnTreatmentLymphoma, Hodgkins / Stage I Adult Hodgkin Lymphoma / Stage II Adult Hodgkin Lymphoma / Stage III Adult Hodgkin Lymphoma / Stage IV Adult Hodgkin Lymphoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral
Capsule, liquid filledOral
SolutionOral
TabletOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6703403Yes1996-12-262016-12-26Us
US6037157Yes1996-12-262016-12-26Us
US6232333Yes1998-05-072018-05-07Us
US7432294Yes2000-11-222020-11-22Us
US7141593Yes2000-11-222020-11-22Us
US5914332Yes1996-06-132016-06-13Us
US6284767Yes1996-08-152016-08-15Us
US7364752Yes2001-05-102021-05-10Us
US8309613Yes2005-06-242025-06-24Us
US8377952Yes2008-04-222028-04-22Us
US8691878Yes2005-02-252025-02-25Us
US8025899Yes2008-06-142028-06-14Us
US7148359Yes2000-01-192020-01-19Us
US8470347Yes2007-03-172027-03-17Us
US8268349Yes2005-02-252025-02-25Us
US8399015Yes2005-02-252025-02-25Us
US6458818Yes1998-05-072018-05-07Us
US6521651Yes1998-05-072018-05-07Us
US6911214Yes2002-05-282022-05-28Us
US8501219No2001-11-282021-11-28Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00192 mg/mLALOGPS
logP3.91ALOGPS
logP4.69ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)13.39ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area120 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity179.36 m3·mol-1ChemAxon
Polarizability69.2 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6593
Blood Brain Barrier-0.9916
Caco-2 permeable+0.8856
P-glycoprotein substrateSubstrate0.8755
P-glycoprotein inhibitor IInhibitor0.7355
P-glycoprotein inhibitor IIInhibitor0.5277
Renal organic cation transporterNon-inhibitor0.8578
CYP450 2C9 substrateNon-substrate0.7508
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6732
CYP450 1A2 substrateNon-inhibitor0.8935
CYP450 2C9 inhibitorNon-inhibitor0.7326
CYP450 2D6 inhibitorNon-inhibitor0.9438
CYP450 2C19 inhibitorNon-inhibitor0.7983
CYP450 3A4 inhibitorNon-inhibitor0.6469
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9054
Ames testNon AMES toxic0.8049
CarcinogenicityNon-carcinogens0.7865
BiodegradationNot ready biodegradable0.9182
Rat acute toxicity2.2503 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8605
hERG inhibition (predictor II)Inhibitor0.8475
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fb9-0119005000-e99616dc321beea979ae
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0532-1900601000-f85a252f1640f27563a8

Taxonomy

Description
This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Valine and derivatives
Alternative Parents
Amphetamines and derivatives / m-Xylenes / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Pyrimidones / Diazinanes / N-acyl amines / Secondary carboxylic acid amides / Ureas
show 7 more
Substituents
Valine or derivatives / Amphetamine or derivatives / Phenoxy compound / Phenol ether / M-xylene / Xylene / Alkyl aryl ether / Pyrimidone / Monocyclic benzene moiety / 1,3-diazinane
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
dicarboxylic acid diamide, amphetamines (CHEBI:31781)

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. Garriga C, Perez-Elias MJ, Delgado R, Ruiz L, Najera R, Pumarola T, Alonso-Socas Mdel M, Garcia-Bujalance S, Menendez-Arias L: Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. J Med Virol. 2007 Nov;79(11):1617-28. [PubMed:17854027]
  2. Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM: Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres. J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. [PubMed:17696512]
  3. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [PubMed:17849388]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. Authors unspecified: Lopinavir/ritonavir: a protease inhibitor combination. Med Lett Drugs Ther. 2001 Jan 8;43(1095):1-2. [PubMed:11151088]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Lopez Aspiroz E, Cabrera Figueroa SE, Iglesias Gomez A, Valverde Merino MP, Dominguez-Gil Hurle A: CYP3A4 polymorphism and lopinavir toxicity in an HIV-infected pregnant woman. Clin Drug Investig. 2015 Jan;35(1):61-6. doi: 10.1007/s40261-014-0245-7. [PubMed:25391550]
  2. Zhou SF: Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab. 2008 May;9(4):310-22. [PubMed:18473749]
  3. Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, Eron JJ Jr, Klein CE, Rublein JC, Kashuba AD: Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr. 2006 May;42(1):52-60. doi: 10.1097/01.qai.0000219774.20174.64. [PubMed:16639344]
  4. Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [PubMed:12724045]
  5. Sham HL, Betebenner DA, Herrin T, Kumar G, Saldivar A, Vasavanonda S, Molla A, Kempf DJ, Plattner JJ, Norbeck DW: Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir). Bioorg Med Chem Lett. 2001 Jun 4;11(11):1351-3. [PubMed:11378352]
  6. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [PubMed:12724045]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [PubMed:12724045]
  2. Kaletra, FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [PubMed:12724045]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [PubMed:12724045]
  2. Hughes CA, Freitas A, Miedzinski LJ: Interaction between lopinavir/ritonavir and warfarin. CMAJ. 2007 Aug 14;177(4):357-9. doi: 10.1503/cmaj.061284. [PubMed:17698824]
  3. Lim ML, Min SS, Eron JJ, Bertz RJ, Robinson M, Gaedigk A, Kashuba AD: Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. J Acquir Immune Defic Syndr. 2004 Aug 15;36(5):1034-40. [PubMed:15247556]
  4. Kaletra FDA label [File]
  5. Cytochrome P450 Enzymes and Transporters Induced by Anti-Human Immunodeficiency Virus Protease Inhibitors in Human Hepatocytes: Implications for Predicting Clinical Drug Interactions [File]
  6. Kaletra EPAR [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:
References
  1. Drug Interactions & Labeling - FDA [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Vishnuvardhan D, Moltke LL, Richert C, Greenblatt DJ: Lopinavir: acute exposure inhibits P-glycoprotein; extended exposure induces P-glycoprotein. AIDS. 2003 May 2;17(7):1092-4. [PubMed:12700464]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [PubMed:20102298]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on August 29, 2007 12:45 / Updated on November 02, 2018 05:03