Identification

Name
Lopinavir
Accession Number
DB01601
Description

Lopinavir is an antiretroviral protease inhibitor used in combination with other antiretrovirals in the treatment of HIV-1 infection.7 Lopinavir is marketed and administered exclusively in combination with ritonavir - this combination, first marketed by Abbott under the brand name Kaletra in 2000, is necessary due to lopinavir's poor oral bioavailability and extensive biotransformation. Ritonavir is a potent inhibitor of the enzymes responsible for lopinavir metabolism, and its co-administration "boosts" lopinavir exposure and improves antiviral activity.7 Like many other protease inhibitors (e.g. saquinavir, nelfinavir), lopinavir is a peptidomimetic molecule - it contains a hydroxyethylene scaffold that mimics the peptide linkage typically targeted by the HIV-1 protease enzyme but which itself cannot be cleaved, thus preventing the activity of the HIV-1 protease.5

Lopinavir is currently under investigation in combination with ritonavir for the treatment of COVID-19 caused by SARS-CoV-2.8

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 628.8008
Monoisotopic: 628.362470666
Chemical Formula
C37H48N4O5
Synonyms
  • Lopinavir
External IDs
  • A-157378-0
  • A-157378.0
  • ABT-378

Pharmacology

Indication

The combination product lopinavir/ritonavir, marketed under the brand name Kaletra, is indicated in combination with other antiretrovirals for the treatment of HIV-1 infection in adults and pediatric patients ≥14 days old.7

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Lopinavir inhibits the activity of an enzyme critical for the HIV viral lifecycle.7 It has a moderate duration of action necessitating once or twice daily dosing.7 Lopinavir, like other protease inhibitors, has a propensity for participating in drug interactions - use caution when administering lopinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common. Fatal hepatotoxicity and pancreatitis have been noted in patients undergoing therapy with lopinavir and patients with an increased baseline risk of these events should be monitored closely throughout therapy.7

Mechanism of action

The HIV lifecycle is comprised of 3 distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious.2 At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV-1 protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle.2

Lopinavir is an inhibitor of the HIV-1 protease enzyme.7 Its design is based on the "peptidomimetic" principle, wherein the molecule contains a hydroxyethylene scaffold which mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved.5 By preventing HIV-1 protease activity, and thus the proteolysis of the Gag polyprotein, lopinavir results in the production of immature, non-infectious viral particles.

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

When administered alone, lopinavir has exceptionally low oral bioavailability (~25%) - for this reason, it is exclusively co-administered with ritonavir, which dramatically improves bioavailability, hinders drug metabolism, and allows for the attainment of therapeutic lopinavir concentrations.3,4 Following oral administration of lopinavir/ritonavir, maximal plasma concentrations are achieved at approximately 4.4 hours (Tmax), and the Cmax and AUCtau are 9.8 ± 3.7 - 11.8 ± 3.7 µg/mL and 92.6 ± 36.7 - 154.1 ± 61.4 μg•h/mL, respectively.7

Relative to administration in the fasted state, administration with a meal increases the AUC of the tablet formulation slightly (~19%) but dramatically increases the AUC of the oral solution formulation (~130%).7

Volume of distribution

The volume of distribution of lopinavir following oral administration is approximately 16.9 L.7

Protein binding

Lopinavir is >98% protein-bound in plasma.7 It binds to both alpha-1-acid glycoprotein and albumin, but exhibits a greater affinity for alpha-1-acid glycoprotein.10

Metabolism

Lopinavir undergoes extensive oxidative metabolism, almost exclusively via hepatic CYP3A isozymes.10 Co-administration with ritonavir, a potent inhibitor of CYP3A enzymes, helps to stave off lopinavir's biotransformation and increase plasma levels of active antiviral drug. Twelve metabolites have been identified in vitro, with the C-4 oxidation products M1, M3, and M4 being the predominant metabolites found in plasma.6 The structures of these primary metabolites have been identified, but precise structural information regarding the remaining minor metabolites has not been elucidated.

Hover over products below to view reaction partners

Route of elimination

Lopinavir is primarily eliminated in the feces. Following oral administration, approximately 10.4 ± 2.3% of the administered dose is excreted in the urine and 82.6 ± 2.5% is excreted in the feces.7 Unchanged parent drug accounted for 2.2% and 19.8% of the administered dose in urine and feces, respectively.10

Half-life

The elimination half-life of lopinavir is 6.9 ± 2.2 hours.7

Clearance

The estimated apparent clearance following oral administration is approximately 6-7 L/h.3,10

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

As lopinavir is only available in combination with ritonavir, experience with acute lopinavir overdose in isolation is limited. The risk related to overdose appears more pronounced in pediatric patients. One case report detailed a fatal cardiogenic shock in a 2.1kg infant following an approximately 10-fold overdose of Kaletra oral solution, while other reported reactions to overdose in infants include complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure. The oral Kaletra solution is highly concentrated, posing a greater risk of overdose, and contains approximately 42% (v/v) ethanol, further increasing risk in children and infants.7

There is no antidote for lopinavir overdose. Treatment of overdose should consist largely of supportive measures and close observation of vital signs and clinical status of the affected patient. Consideration should be given to the removal of unabsorbed drug using gastric lavage or activated charcoal, if clinically indicated. Dialysis is unlikely to be of benefit as lopinavir is highly protein-bound, but may help to remove ethanol and propylene glycol from the circulation in the case of overdose with Kaletra oral solution.7

Affected organisms
  • Human Immunodeficiency Virus
  • SARS-CoV-2
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Lopinavir.
AbametapirThe serum concentration of Lopinavir can be increased when it is combined with Abametapir.
AbataceptThe serum concentration of Abatacept can be increased when it is combined with Lopinavir.
AbemaciclibThe metabolism of Lopinavir can be decreased when combined with Abemaciclib.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Lopinavir.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Lopinavir.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Lopinavir.
AcebutololThe risk or severity of QTc prolongation can be increased when Lopinavir is combined with Acebutolol.
AceclofenacLopinavir may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Lopinavir is combined with Acemetacin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid St. John's Wort. Induction of CYP3A by co-administration with St. John's Wort may result in reduced drug plasma concentrations and therapeutic failure.
  • Take with food. The oral solution formulation must be taken with food, but the tablet formulation may be taken with or without food.

Products

International/Other Brands
Aluviran / Koletra
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
KaletraLopinavir (100 mg/1) + Ritonavir (25 mg/1)Tablet, film coatedOralAbbVie Inc.2010-06-18Not applicableUs
KaletraLopinavir (200 mg) + Ritonavir (50 mg)TabletOralAbbvie2006-09-08Not applicableCanada
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralAbbVie Inc.2020-04-08Not applicableUs
KaletraLopinavir (133.3 mg/1) + Ritonavir (33.3 mg/1)Capsule, liquid filledOralAbbVie Inc.2000-09-152009-06-01Us
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralHHS/Program Support Center/Supply Service Center2010-06-18Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralA-S Medication Solutions2010-06-18Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralREMEDYREPACK INC.2016-12-29Not applicableUs
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralCardinal Health2010-06-182016-01-31Us
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)Tablet, film coatedOralAbbVie Inc.2010-06-18Not applicableUs
KaletraLopinavir (400 mg) + Ritonavir (100 mg)SolutionOralAbbvie2001-03-09Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
KaletraLopinavir (200 mg/1) + Ritonavir (50 mg/1)TabletOralRemedy Repack2010-09-272013-05-16Us

Categories

ATC Codes
J05AR10 — Lopinavir and ritonavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,3-diazinane / Alcohol / Alkyl aryl ether / Amphetamine or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxamide group
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
dicarboxylic acid diamide, amphetamines (CHEBI:31781)

Chemical Identifiers

UNII
2494G1JF75
CAS number
192725-17-0
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

References

Synthesis Reference
US5914332
General References
  1. Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [PubMed:21953914]
  2. Sundquist WI, Krausslich HG: HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006924. doi: 10.1101/cshperspect.a006924. [PubMed:22762019]
  3. Niu WJ, Sun T, Liu L, Liu XQ, Zhang RF, Yin L, Wang JR, Jia XF, Lu HZ, Zhong MK, Jiao Z, Zhang LJ: Population pharmacokinetics and dosing regimen optimisation of lopinavir in Chinese adults infected with HIV. Basic Clin Pharmacol Toxicol. 2019 Apr;124(4):456-465. doi: 10.1111/bcpt.13154. Epub 2018 Nov 23. [PubMed:30346663]
  4. Sham HL, Kempf DJ, Molla A, Marsh KC, Kumar GN, Chen CM, Kati W, Stewart K, Lal R, Hsu A, Betebenner D, Korneyeva M, Vasavanonda S, McDonald E, Saldivar A, Wideburg N, Chen X, Niu P, Park C, Jayanti V, Grabowski B, Granneman GR, Sun E, Japour AJ, Leonard JM, Plattner JJ, Norbeck DW: ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother. 1998 Dec;42(12):3218-24. [PubMed:9835517]
  5. De Clercq E: Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20. doi: 10.1016/j.ijantimicag.2008.10.010. Epub 2008 Dec 23. [PubMed:19108994]
  6. Kumar GN, Jayanti V, Lee RD, Whittern DN, Uchic J, Thomas S, Johnson P, Grabowski B, Sham H, Betebenner D, Kempf DJ, Denissen JF: In vitro metabolism of the HIV-1 protease inhibitor ABT-378: species comparison and metabolite identification. Drug Metab Dispos. 1999 Jan;27(1):86-91. [PubMed:9884314]
  7. FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]
  8. Nature Biotechnology: Coronavirus puts drug repurposing on the fast track [Link]
  9. CaymanChem: Lopinavir MSDS [Link]
  10. Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
Human Metabolome Database
HMDB0015539
KEGG Drug
D01425
KEGG Compound
C12871
PubChem Compound
92727
PubChem Substance
46508588
ChemSpider
83706
BindingDB
50180655
RxNav
195088
ChEBI
31781
ChEMBL
CHEMBL729
ZINC
ZINC000003951740
Therapeutic Targets Database
DAP000708
PharmGKB
PA450264
PDBe Ligand
AB1
RxList
RxList Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Lopinavir
PDB Entries
1mui / 1rv7 / 2o4s / 2q5k / 2qhc / 2rkf / 2rkg / 2z54 / 3ogq / 4l1a
show 3 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Proteinuria1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis (TB)1
4CompletedBasic ScienceCardiovascular Heart Disease / Dyslipidemia / 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) Infections6
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
Capsule, liquid filledOral
TabletOral
Tablet, film coatedOral
GranuleOral
SolutionOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6703403Yes2004-03-092016-12-26Us
US6037157Yes2000-03-142016-12-26Us
US6232333Yes2001-05-152018-05-07Us
US7432294Yes2008-10-072020-11-22Us
US7141593Yes2006-11-282020-11-22Us
US5914332Yes1999-06-222016-06-13Us
US6284767Yes2001-09-042016-08-15Us
US7364752Yes2008-04-292021-05-10Us
US8309613Yes2012-11-132025-06-24Us
US8377952Yes2013-02-192028-04-22Us
US8691878Yes2014-04-082025-02-25Us
US8025899Yes2011-09-272028-06-14Us
US7148359Yes2006-12-122020-01-19Us
US8470347Yes2013-06-252027-03-17Us
US8268349Yes2012-09-182025-02-25Us
US8399015Yes2013-03-192025-02-25Us
US6458818Yes2002-10-012018-05-07Us
US6521651Yes2003-02-182018-05-07Us
US6911214Yes2005-06-282022-05-28Us
US8501219No2013-08-062021-11-28Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleHealth Canada Monograph
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
Polarizability68.78 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

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
Humans
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. 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]
  2. 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]
  3. 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]
  4. Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [PubMed:21953914]
  5. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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]
  2. Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [PubMed:21953914]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [PubMed:21953914]
  2. 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
Humans
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
Humans
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
Humans
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 group
Organism
Humans
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. 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. FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
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]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]
Kind
Protein
Organism
Humans
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. 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]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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 June 12, 2020 11:41

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