Identification
- Name
- Lopinavir
- Accession Number
- DB01601 (EXPT00388)
- Type
- Small Molecule
- Groups
- Approved
- 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
- Structure
Structure for Lopinavir (DB01601)
- Synonyms
- Lopinavir
- External IDs
- A-157378-0 / A-157378.0 / ABT-378
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral AbbVie Inc. 2010-06-18 Not applicable US 
Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral AbbVie Inc. 2020-04-08 Not applicable US Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral Physicians Total Care, Inc. 2006-04-11 Not applicable US Kaletra Lopinavir (80 mg/1mL) + Ritonavir (20 mg/1mL) Solution Oral AbbVie Inc. 2010-06-18 Not applicable US Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral Rebel Distributors 2010-06-18 Not applicable US Kaletra Lopinavir (100 mg/1) + Ritonavir (25 mg/1) Tablet, film coated Oral AbbVie Inc. 2010-06-18 Not applicable US Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral REMEDYREPACK INC. 2016-12-29 Not applicable US Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral PD-Rx Pharmaceuticals, Inc. 2010-06-18 Not applicable US Kaletra Lopinavir (133.3 mg/1) + Ritonavir (33.3 mg/1) Capsule, liquid filled Oral Abbvie 2000-09-15 2005-12-21 US Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral Doh Central Pharmacy 2009-07-01 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet Oral Remedy Repack 2010-09-27 2013-05-16 US - International/Other Brands
- Aluviran / Koletra
- Categories
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- BSEP/ABCB11 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Experimental Unapproved Treatments for COVID-19
- HIV Protease Inhibitors
- Hyperglycemia-Associated Agents
- Nephrotoxic agents
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- Potential QTc-Prolonging Agents
- Protease Inhibitors
- Pyrimidinones
- QTc Prolonging Agents
- 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
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
- 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.
Target Actions Organism AHuman immunodeficiency virus type 1 protease inhibitorHuman 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.
- 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
- 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
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Learn moreStructured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Learn moreStructured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Learn moreInteractions
- 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.
Drug Interaction Unlock Additional Data(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Lopinavir. (S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Lopinavir. 2-Methoxyethanol The serum concentration of 2-Methoxyethanol can be increased when it is combined with Lopinavir. 2,4-thiazolidinedione The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Lopinavir. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Lopinavir. 9-(N-methyl-L-isoleucine)-cyclosporin A The serum concentration of 9-(N-methyl-L-isoleucine)-cyclosporin A can be increased when it is combined with Lopinavir. 9-aminocamptothecin The metabolism of Lopinavir can be decreased when combined with 9-aminocamptothecin. Abacavir The serum concentration of Abacavir can be decreased when it is combined with Lopinavir. Abatacept The serum concentration of Abatacept can be increased when it is combined with Lopinavir. Abemaciclib The metabolism of Lopinavir can be decreased when combined with Abemaciclib. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- 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.
References
- Synthesis Reference
- US5914332
- General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]
- Nature Biotechnology: Coronavirus puts drug repurposing on the fast track [Link]
- CaymanChem: Lopinavir MSDS [Link]
- Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
- External Links
- 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
- 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
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Capsule Oral Capsule, liquid filled Oral Tablet Oral Tablet, film coated Oral Granule Oral Solution Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Unlock Additional DataUS6703403 Yes 2004-03-09 2016-12-26 US US6037157 Yes 2000-03-14 2016-12-26 US US6232333 Yes 2001-05-15 2018-05-07 US US7432294 Yes 2008-10-07 2020-11-22 US US7141593 Yes 2006-11-28 2020-11-22 US US5914332 Yes 1999-06-22 2016-06-13 US US6284767 Yes 2001-09-04 2016-08-15 US US7364752 Yes 2008-04-29 2021-05-10 US US8309613 Yes 2012-11-13 2025-06-24 US US8377952 Yes 2013-02-19 2028-04-22 US US8691878 Yes 2014-04-08 2025-02-25 US US8025899 Yes 2011-09-27 2028-06-14 US US7148359 Yes 2006-12-12 2020-01-19 US US8470347 Yes 2013-06-25 2027-03-17 US US8268349 Yes 2012-09-18 2025-02-25 US US8399015 Yes 2013-03-19 2025-02-25 US US6458818 Yes 2002-10-01 2018-05-07 US US6521651 Yes 2003-02-18 2018-05-07 US US6911214 Yes 2005-06-28 2022-05-28 US US8501219 No 2013-08-06 2021-11-28 US Additional Data Available- Filed On
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Practically insoluble Health Canada Monograph - Predicted Properties
Property Value Source Water Solubility 0.00192 mg/mL ALOGPS logP 3.91 ALOGPS logP 4.69 ChemAxon logS -5.5 ALOGPS pKa (Strongest Acidic) 13.39 ChemAxon pKa (Strongest Basic) -1.5 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 120 Å2 ChemAxon Rotatable Bond Count 15 ChemAxon Refractivity 179.36 m3·mol-1 ChemAxon Polarizability 68.78 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption - 0.6593 Blood Brain Barrier - 0.9916 Caco-2 permeable + 0.8856 P-glycoprotein substrate Substrate 0.8755 P-glycoprotein inhibitor I Inhibitor 0.7355 P-glycoprotein inhibitor II Inhibitor 0.5277 Renal organic cation transporter Non-inhibitor 0.8578 CYP450 2C9 substrate Non-substrate 0.7508 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6732 CYP450 1A2 substrate Non-inhibitor 0.8935 CYP450 2C9 inhibitor Non-inhibitor 0.7326 CYP450 2D6 inhibitor Non-inhibitor 0.9438 CYP450 2C19 inhibitor Non-inhibitor 0.7983 CYP450 3A4 inhibitor Non-inhibitor 0.6469 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9054 Ames test Non AMES toxic 0.8049 Carcinogenicity Non-carcinogens 0.7865 Biodegradation Not ready biodegradable 0.9182 Rat acute toxicity 2.2503 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8605 hERG inhibition (predictor II) Inhibitor 0.8475
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0fb9-0119005000-e99616dc321beea979ae MS/MS Spectrum - , positive LC-MS/MS splash10-0532-1900601000-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
- 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]
- 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]
- 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]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Authors unspecified: Lopinavir/ritonavir: a protease inhibitor combination. Med Lett Drugs Ther. 2001 Jan 8;43(1095):1-2. [PubMed:11151088]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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]
- 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]
- 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]
- 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]
- 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
- 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]
- 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
- SubstrateInhibitor
- 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
- 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]
- 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
- 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]
- 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
- 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
- InhibitorInducer
- 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
- 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]
- 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]
- 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]
- Kaletra FDA label [File]
- Cytochrome P450 Enzymes and Transporters Induced by Anti-Human Immunodeficiency Virus Protease Inhibitors in Human Hepatocytes: Implications for Predicting Clinical Drug Interactions [File]
- 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:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- 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]
- 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
- 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
- Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- 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
- 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]
- 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
- 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]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- 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
- 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]
- 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
- 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 May 02, 2020 03:32
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