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Identification
NameValproic Acid
Accession NumberDB00313  (APRD00066, APRD00256, DB00510)
Typesmall molecule
Groupsapproved, investigational
Description

Valproic acid, supplied as the sodium salt valproate semisodium or divalproex sodium, is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage dependent sodium channels. Typically supplied in the sodium salt form (CAS number: 76584-70-8). Valproic Acid is also a histone deacetylase inhibitor and is under investigation for treatment of HIV and various cancers.

Structure
Thumb
Synonyms
SynonymLanguageCode
2-n-propyl-n-valeric acidNot AvailableNot Available
2-Propylpentanoic AcidNot AvailableNot Available
2-Propylvaleric AcidNot AvailableNot Available
4-heptanecarboxylic acidNot AvailableNot Available
di-n-propylacetic acidNot AvailableNot Available
Di-n-propylessigsäureGermanNot Available
Dipropylacetic acidNot AvailableNot Available
DPANot AvailableNot Available
n-DPANot AvailableNot Available
ValproateNot AvailableNot Available
ValproinsäureGermanNot Available
VPANot AvailableNot Available
Salts
Name/CAS Structure Properties
Valproate Semisodium
76584-70-8
Thumb
  • InChI Key: MSRILKIQRXUYCT-UHFFFAOYSA-M
  • Monoisotopic Mass: 310.212004155
  • Average Mass: 310.4047
DBSALT000185
Brand names
NameCompany
ConvulexNot Available
DepaconNot Available
DepakeneNot Available
DepakineNot Available
DepakoteNot Available
Depakote ERNot Available
DeprakineNot Available
EncorateNot Available
EpilimNot Available
EpivalNot Available
StavzorNot Available
ValcoteNot Available
ValparinNot Available
Brand mixturesNot Available
Categories
CAS number99-66-1
WeightAverage: 144.2114
Monoisotopic: 144.115029756
Chemical FormulaC8H16O2
InChI KeyInChIKey=NIJJYAXOARWZEE-UHFFFAOYSA-N
InChI
InChI=1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)
IUPAC Name
2-propylpentanoic acid
SMILES
CCCC(CCC)C(O)=O
Mass Specshow(8.07 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsEnolates; Carboxylic Acids
SubstituentsNot Available
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationFor treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome.
PharmacodynamicsThe relationship between plasma concentration and clinical response is not well documented. One contributing factor is the nonlinear, concentration dependent protein binding of valproate which affects the clearance of the drug. Thus, monitoring of total serum valproate cannot provide a reliable index of the bioactive valproate species. For patients with epilepsy, the therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. However, patients may be controlled at lower or higher doses.
Mechanism of actionValproic Acid dissociates to the valproate ion in the gastrointestinal tract and then binds to and inhibits GABA transaminase. The drug's anticonvulsant activity may be related to increased brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. It is also a histone deacetylase inhibitor. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection.
AbsorptionRapid absorption from gastrointestinal tract. Although the rate of valproate ion absorption may vary with the formulation administered (liquid, solid, or sprinkle), conditions of use (e.g., fasting or postprandial) and the method of administration (e.g., whether the contents of the capsule are sprinkled on food or the capsule is taken intact), these differences should be of minor clinical importance under the steady state conditions achieved in chronic use in the treatment of epilepsy. Food has a greater influence on the rate of absorption of the Depakote tablet (increases Tmax from 4 to 8 hours) than on the absorption of Depakote sprinkle capsules (increase Tmax from 3.3 to 4.8 hours). Furthermore, studies suggest that total daily systemic bioavailability (extent of absorption) is the primary determinant of seizure control.
Volume of distribution
  • 11 L/1.73 m2 [total valproate]
  • 92 L/1.73 m2 [free valproate]
Protein bindingConcentration-dependent, from 90% at 40 µg/mL to 81.5% at 130 µg/mL. Higher than expected free fractions occur in the elderly, in hyperlipidemic patients, and in patients with hepatic and renal diseases. It may also affect the extent of protein binding of other drugs such as phenytoin or carbamazepine.
Metabolism

Valproic Acid is metabolized almost entirely by the liver. In adult patients on monotherapy, 30-50% of an administered dose appears in urine as a glucuronide conjugate. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose. Usually, less than 15-20% of the dose is eliminated by other oxidative mechanisms. Less than 3% of an administered dose is excreted unchanged in urine.

SubstrateEnzymesProduct
Valproic Acid
4-ene-Valproic acidDetails
Valproic Acid
5-Hydroxyvalproic acidDetails
Valproic Acid
3-Hydroxyvalproic acidDetails
Valproic Acid
4-Hydroxyvalproic acidDetails
Valproic Acid
Valproic acid β-O-glucuronideDetails
Valproic Acid
    2-ene-Valproic acidDetails
    Valproic Acid
      (3Z)-2-Propylpent-3-enoic acid (3Z-Ene-VPA)Details
      Valproic Acid
        (3E)-2-Propylpent-3-enoic acid (3E-Ene-VPA)Details
        Valproic Acid
          Valproic acid CoADetails
          4-ene-Valproic acid
            2,4-Diene-VPADetails
            4-Hydroxyvalproic acid
              2-n-Propyl-4-oxopentanoic acidDetails
              2-n-Propyl-4-oxopentanoic acid
                2-Propylsuccinic acidDetails
                5-Hydroxyvalproic acid
                  2-Propylglutaric acidDetails
                  3-Hydroxyvalproic acid
                    3-Oxovalproic acidDetails
                    2-ene-Valproic acid
                      3-Hydroxyvalproic acidDetails
                      3-Hydroxyvalproic acid
                        3-Oxovalproic acidDetails
                        Route of eliminationValproate is metabolized almost entirely by the liver. Less than 3% of an administered dose is excreted unchanged in urine. Mitochondrial ß-oxidation is the other major metabolic pathway, typically accounting for over 40% of the dose.
                        Half life9-16 hours (following oral administration of 250 mg to 1000 mg)
                        Clearance
                        • 0.56 L/hr/1.73 m2 [plasma clearance, total valproate]
                        • 4.6 L/hr/1.73 m2 [plasma clearance, free valproate]
                        • 4.8 ± 0.17 L/hr/1.73 m2 [males, unbound clearance]
                        • 4.7 ± 0.07 L/hr/1.73 m2 [females, unbound clearance]
                        ToxicityOral, mouse: LD50 = 1098 mg/kg; Oral, rat: LD50 = 670 mg/kg. Symptoms of overdose may include coma, extreme drowsiness, and heart problems. The safety and tolerability of valproate in pediatric patients were shown to be comparable to those in adults.
                        Affected organisms
                        • Humans and other mammals
                        PathwaysNot Available
                        SNP Mediated EffectsNot Available
                        SNP Mediated Adverse Drug ReactionsNot Available
                        ADMET
                        Predicted ADMET features
                        Property Value Probability
                        Human Intestinal Absorption + 0.9828
                        Blood Brain Barrier + 0.9626
                        Caco-2 permeable + 0.8866
                        P-glycoprotein substrate Non-substrate 0.7345
                        P-glycoprotein inhibitor I Non-inhibitor 0.9695
                        P-glycoprotein inhibitor II Non-inhibitor 0.7405
                        Renal organic cation transporter Non-inhibitor 0.9277
                        CYP450 2C9 substrate Non-substrate 0.8247
                        CYP450 2D6 substrate Non-substrate 0.9115
                        CYP450 3A4 substrate Non-substrate 0.7033
                        CYP450 1A2 substrate Non-inhibitor 0.5447
                        CYP450 2C9 substrate Non-inhibitor 0.8174
                        CYP450 2D6 substrate Non-inhibitor 0.9397
                        CYP450 2C19 substrate Non-inhibitor 0.957
                        CYP450 3A4 substrate Non-inhibitor 0.9583
                        CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9364
                        Ames test Non AMES toxic 0.9805
                        Carcinogenicity Non-carcinogens 0.5266
                        Biodegradation Ready biodegradable 0.8523
                        Rat acute toxicity 1.8543 LD50, mol/kg Not applicable
                        hERG inhibition (predictor I) Weak inhibitor 0.9357
                        hERG inhibition (predictor II) Non-inhibitor 0.9249
                        Pharmacoeconomics
                        Manufacturers
                        • Banner pharmacaps inc
                        • Abbott laboratories pharmaceutical products div
                        • Catalent pharma solutions llc
                        • Par pharmaceutical inc
                        • Rp scherer north america div rp scherer corp
                        • Usl pharma inc
                        • Alpharma uspd inc
                        • Apotex inc richmond hill
                        • High technology pharmacal co inc
                        • Pharmaceutical assoc inc div beach products
                        • Sun pharmaceutical industries inc
                        • Teva pharmaceuticals usa
                        • Vintage pharmaceuticals llc
                        • Wockhardt eu operations (swiss) ag
                        Packagers
                        Dosage forms
                        FormRouteStrength
                        CapsuleOral250 mg
                        Capsule, delayed releaseOral125 mg, 250 mg, 500 mg
                        Injection, solutionIntravenous100 mg/mL
                        SolutionOral250 mg/5 mL
                        SyrupOral250 mg/mL
                        Tablet, delayed releaseOral125 mg, 250 mg, 500 mg
                        Tablet, extended releaseOral250 mg, 500 mg
                        Prices
                        Unit descriptionCostUnit
                        Valproic acid liquid10.2USDg
                        Depakene 250 mg capsule2.21USDcapsule
                        Valproic acid 250 mg capsule0.79USDcapsule
                        Depakene 250 mg/5ml Syrup0.66USDml
                        Novo-Valproic 500 mg Enteric-Coated Capsule0.54USDcapsule
                        Pms-Valproic Acid E.C. 500 mg Enteric-Coated Capsule0.54USDcapsule
                        Apo-Valproic 250 mg Capsule0.27USDcapsule
                        Mylan-Valproic 250 mg Capsule0.27USDcapsule
                        Novo-Valproic 250 mg Capsule0.27USDcapsule
                        Nu-Valproic 250 mg Capsule0.27USDcapsule
                        Pms-Valproic Acid 250 mg Capsule0.27USDcapsule
                        Ratio-Valproic 250 mg Capsule0.27USDcapsule
                        Sandoz Valproic 250 mg Capsule0.27USDcapsule
                        Valproic Acid 250 mg/5ml Syrup0.16USDml
                        Valproic acid 250 mg/5 ml syr0.15USDml
                        Depakene 50 mg/ml Syrup0.11USDml
                        Apo-Valproic 50 mg/ml Syrup0.06USDml
                        Pms-Valproic Acid 50 mg/ml Syrup0.06USDml
                        Ratio-Valproic 50 mg/ml Syrup0.06USDml
                        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
                        Patents
                        CountryPatent NumberApprovedExpires (estimated)
                        United States65116781999-06-182019-06-18
                        Properties
                        Statesolid
                        Experimental Properties
                        PropertyValueSource
                        melting point120-130 °CNot Available
                        water solubility1.3 mg/mLFDA label
                        logP2.75SANGSTER (1993)
                        logS-1.86ADME Research, USCD
                        pKa4.8FDA label
                        Predicted Properties
                        PropertyValueSource
                        water solubility2.36e+00 g/lALOGPS
                        logP2.54ALOGPS
                        logP2.8ChemAxon
                        logS-1.8ALOGPS
                        pKa (strongest acidic)5.14ChemAxon
                        physiological charge-1ChemAxon
                        hydrogen acceptor count2ChemAxon
                        hydrogen donor count1ChemAxon
                        polar surface area37.3ChemAxon
                        rotatable bond count5ChemAxon
                        refractivity40.25ChemAxon
                        polarizability17ChemAxon
                        number of rings0ChemAxon
                        bioavailability1ChemAxon
                        rule of fiveYesChemAxon
                        Ghose filterNoChemAxon
                        Veber's ruleYesChemAxon
                        MDDR-like ruleNoChemAxon
                        Spectra
                        Spectra
                        References
                        Synthesis Reference

                        Daniel Aubert, Francis Blanc, Henri Desmolin, Michel Morre, Lucette Sindely, “Valproic acid preparations.” U.S. Patent US5017613, issued January, 1965.

                        US5017613
                        General Reference
                        1. Rosenberg G: The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007 Aug;64(16):2090-103. Pubmed
                        2. Lehrman G, Hogue IB, Palmer S, Jennings C, Spina CA, Wiegand A, Landay AL, Coombs RW, Richman DD, Mellors JW, Coffin JM, Bosch RJ, Margolis DM: Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet. 2005 Aug 13-19;366(9485):549-55. Pubmed
                        3. Schwartz C, Palissot V, Aouali N, Wack S, Brons NH, Leners B, Bosseler M, Berchem G: Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines. Int J Oncol. 2007 Mar;30(3):573-82. Pubmed
                        4. Valentini A, Gravina P, Federici G, Bernardini S: Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells. Cancer Biol Ther. 2007 Feb;6(2):185-91. Epub 2007 Feb 5. Pubmed
                        5. FDA label
                        External Links
                        ResourceLink
                        KEGG DrugD00399
                        KEGG CompoundC07185
                        PubChem Compound3121
                        PubChem Substance46505925
                        ChemSpider3009
                        ChEBI9926
                        ChEMBLCHEMBL109
                        Therapeutic Targets DatabaseDNC001659
                        PharmGKBPA451846
                        Drug Product Database2260654
                        RxListhttp://www.rxlist.com/cgi/generic2/depakene.htm
                        Drugs.comhttp://www.drugs.com/cdi/valproate.html
                        PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dep1124.shtml
                        WikipediaValproic_Acid
                        ATC CodesN03AG01
                        AHFS Codes
                        • 28:12.92
                        PDB Entries
                        FDA labelshow(1.41 MB)
                        MSDSshow(77.9 KB)
                        Interactions
                        Drug Interactions
                        Drug
                        Acetylsalicylic acidAcetylsalicylic acid increases the effect of valproic acid.
                        AsenapineValproate completely inhibits the glucuronidation of asenapine but does not effect its exposure. Dose adjustment is not necessary with concomitant therapy.
                        CarbamazepineDecreases the effect of valproic acid
                        ClarithromycinThe macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Clarithromycin is initiated, discontinued or dose changed.
                        EltrombopagAffects hepatic CYP2C9/10 metabolism, will increase effect/level of eltrombopag.
                        ErythromycinThe macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Erythromycin is initiated, discontinued or dose changed.
                        FelbamateFelbamate, a CYP2C19 inhibitor, may decrease the metabolism of Valproic acid, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Felbamate is initiated, discontinued or dose changed.
                        Glycerol PhenylbutyrateValproic acid may induce hyperammonemia. Monitor ammonia levels closely when use of valproic acid is necessary in UCD patients.
                        LacosamideValproic acid toxicity may occur at any time during the treatment course and should be considered in patients with acute changes in mentation, especially if there has been a recent change in antiepileptic therapy.
                        LamotrigineValproic acid may increase the adverse effects of Lamotrigine by increasing Lamotrigine serum concentration. The Lamotrigine dose should be reduced by 50% during concomitant therapy. Monitor for changes in Lamotrigine therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed.
                        LorazepamValproic acid may increase the serum concentration of Lorazepam by reducing Lorazepam metabolism. The Lorazepam dose should be reduced by 50% during concomitant therapy. Monitor for increased Lorazepam effects and toxicity.
                        NimodipineValproic acid increases the effect of nimodipine
                        RifampicinRifampin may reduce the serum concentration of Valproic acid by increasing Valproic acid metabolism. Valproic acid dose adjustments may be required during concomitant therapy. Monitor Valproic acid serum concentrations, efficacy and toxicity if Rifampin is initiated, discontinued or dose changed.
                        RufinamideValproic acid may increase the therapeutic/toxic effects of Rufinamide. Consider alternate therapy or monitor for changes in Rufinamide serum concentrations, therapeutic and adverse effects if Valproic acid is initiated, discontinued or dose changed. Decreases clearance of rufinamide and is a selective inhibitor of human carboxylesterase thus increasing serum concentrations.
                        SilodosinStrong UGT2B7 inhibitors may increase levels of silodosin. Monitor concomitant therapy closely.
                        TelithromycinThe macrolide antibiotic, Erythromycin, may increase the serum concentratin of Valproic acid. Consider alternate therapy or monitor for changes in Valproic acid therapeutic and adverse effects if Telithromycin is initiated, discontinued or dose changed.
                        TipranavirTipranavir decreases the concentration of Valproic acid. Monitor Valproid acid efficacy.
                        VigabatrinVigabatrin reduces serum concentrations of valproic acid by 8%.
                        Food Interactions
                        • Avoid alcohol.
                        • Do not take with milk.
                        • Take with food.

                        1. Histone deacetylase 9

                        Kind: protein

                        Organism: Human

                        Pharmacological action: yes

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Histone deacetylase 9 Q9UKV0 Details

                        References:

                        1. Ylisastigui L, Archin NM, Lehrman G, Bosch RJ, Margolis DM: Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS. 2004 May 21;18(8):1101-8. Pubmed
                        2. Michaelis M, Kohler N, Reinisch A, Eikel D, Gravemann U, Doerr HW, Nau H, Cinatl J Jr: Increased human cytomegalovirus replication in fibroblasts after treatment with therapeutical plasma concentrations of valproic acid. Biochem Pharmacol. 2004 Aug 1;68(3):531-8. Pubmed
                        3. Kanai H, Sawa A, Chen RW, Leeds P, Chuang DM: Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. Pharmacogenomics J. 2004;4(5):336-44. Pubmed
                        4. Stockhausen MT, Sjolund J, Manetopoulos C, Axelson H: Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells. Br J Cancer. 2005 Feb 28;92(4):751-9. Pubmed
                        5. Beutler AS, Li S, Nicol R, Walsh MJ: Carbamazepine is an inhibitor of histone deacetylases. Life Sci. 2005 May 13;76(26):3107-15. Pubmed
                        6. Rosenberg G: The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007 Aug;64(16):2090-103. Pubmed
                        7. Kawano T, Akiyama M, Agawa-Ohta M, Mikami-Terao Y, Iwase S, Yanagisawa T, Ida H, Agata N, Yamada H: Histone deacetylase inhibitors valproic acid and depsipeptide sensitize retinoblastoma cells to radiotherapy by increasing H2AX phosphorylation and p53 acetylation-phosphorylation. Int J Oncol. 2010 Oct;37(4):787-95. Pubmed

                        2. 4-aminobutyrate aminotransferase, mitochondrial

                        Kind: protein

                        Organism: Human

                        Pharmacological action: yes

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        4-aminobutyrate aminotransferase, mitochondrial P80404 Details

                        References:

                        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
                        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
                        3. Loscher W: Anticonvulsant and biochemical effects of inhibitors of GABA aminotransferase and valproic acid during subchronic treatment in mice. Biochem Pharmacol. 1982 Mar 1;31(5):837-42. Pubmed
                        4. Ha JH, Lee DU, Lee JT, Kim JS, Yong CS, Kim JA, Ha JS, Huh K: 4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain. J Ethnopharmacol. 2000 Nov;73(1-2):329-33. Pubmed
                        5. Semba J, Kuroda Y, Takahashi R: Potential antidepressant properties of subchronic GABA transaminase inhibitors in the forced swimming test in mice. Neuropsychobiology. 1989;21(3):152-6. Pubmed
                        6. Rosenberg G: The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci. 2007 Aug;64(16):2090-103. Pubmed

                        3. Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial P45954 Details

                        References:

                        1. Ito M, Ikeda Y, Arnez JG, Finocchiaro G, Tanaka K: The enzymatic basis for the metabolism and inhibitory effects of valproic acid: dehydrogenation of valproyl-CoA by 2-methyl-branched-chain acyl-CoA dehydrogenase. Biochim Biophys Acta. 1990 May 16;1034(2):213-8. Pubmed
                        2. Bazinet RP, Weis MT, Rapoport SI, Rosenberger TA: Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder. Psychopharmacology (Berl). 2006 Jan;184(1):122-9. Epub 2005 Dec 13. Pubmed

                        4. 2-oxoglutarate dehydrogenase, mitochondrial

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        2-oxoglutarate dehydrogenase, mitochondrial Q02218 Details

                        References:

                        1. Johannessen CU, Johannessen SI: Valproate: past, present, and future. CNS Drug Rev. 2003 Summer;9(2):199-216. Pubmed

                        5. Succinate-semialdehyde dehydrogenase, mitochondrial

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Succinate-semialdehyde dehydrogenase, mitochondrial P51649 Details

                        References:

                        1. Johannessen CU, Johannessen SI: Valproate: past, present, and future. CNS Drug Rev. 2003 Summer;9(2):199-216. Pubmed

                        1. Cytochrome P450 2A6

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate inducer

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 2A6 P11509 Details

                        References:

                        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
                        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
                        3. Lexicomp

                        2. Cytochrome P450 2B6

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 2B6 P20813 Details

                        References:

                        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

                        3. Cytochrome P450 2C9

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate inhibitor

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 2C9 P11712 Details

                        References:

                        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
                        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
                        3. Lexicomp

                        4. Cytochrome P450 3A5

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 3A5 P20815 Details

                        References:

                        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

                        5. Prostaglandin G/H synthase 1

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        Prostaglandin G/H synthase 1 P23219 Details

                        References:

                        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

                        6. Cytochrome P450 1A2

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 1A2 P05177 Details

                        References:

                        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

                        7. Cytochrome P450 2C18

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 2C18 P33260 Details

                        References:

                        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

                        8. Cytochrome P450 2C19

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate inhibitor

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 2C19 P33261 Details

                        References:

                        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

                        9. Cytochrome P450 2C8

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 2C8 P10632 Details

                        References:

                        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

                        10. Cytochrome P450 3A4

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Cytochrome P450 3A4 P08684 Details

                        References:

                        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

                        11. UDP-glucuronosyltransferase 1-4

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 1-4 P22310 Details

                        References:

                        1. Argikar UA, Remmel RP: Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36. doi: 10.1124/dmd.108.022426. Epub 2008 Oct 6. Pubmed

                        12. UDP-glucuronosyltransferase 1-8

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 1-8 Q9HAW9 Details

                        References:

                        1. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH: UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. Epub 2005 Mar 10. Pubmed

                        13. UDP-glucuronosyltransferase 1-10

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 1-10 Q9HAW8 Details

                        References:

                        1. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH: UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. Epub 2005 Mar 10. Pubmed

                        14. UDP-glucuronosyltransferase 1-6

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 1-6 P19224 Details

                        References:

                        1. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH: UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. Epub 2005 Mar 10. Pubmed

                        15. UDP-glucuronosyltransferase 1-3

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 1-3 P35503 Details

                        References:

                        1. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH: UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6. Epub 2005 Mar 10. Pubmed
                        2. Argikar UA, Remmel RP: Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36. doi: 10.1124/dmd.108.022426. Epub 2008 Oct 6. Pubmed
                        3. Chung JY, Cho JY, Yu KS, Kim JR, Lim KS, Sohn DR, Shin SG, Jang IJ: Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600. Epub 2007 Aug 8. Pubmed

                        16. UDP-glucuronosyltransferase 2B7

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 2B7 P16662 Details

                        References:

                        1. Chung JY, Cho JY, Yu KS, Kim JR, Lim KS, Sohn DR, Shin SG, Jang IJ: Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600. Epub 2007 Aug 8. Pubmed

                        17. UDP-glucuronosyltransferase 2B15

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 2B15 P54855 Details

                        References:

                        1. Chung JY, Cho JY, Yu KS, Kim JR, Lim KS, Sohn DR, Shin SG, Jang IJ: Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600. Epub 2007 Aug 8. Pubmed

                        18. UDP-glucuronosyltransferase 1-9

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        UDP-glucuronosyltransferase 1-9 O60656 Details

                        References:

                        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

                        1. Solute carrier family 22 member 6

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Solute carrier family 22 member 6 Q4U2R8 Details

                        References:

                        1. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H: Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997 Jul 25;272(30):18526-9. Pubmed

                        2. Solute carrier family 22 member 5

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: inhibitor

                        Components

                        Name UniProt ID Details
                        Solute carrier family 22 member 5 O76082 Details

                        References:

                        1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

                        3. Solute carrier family 22 member 8

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate inhibitor

                        Components

                        Name UniProt ID Details
                        Solute carrier family 22 member 8 Q8TCC7 Details

                        References:

                        1. Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T: Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem. 2002 Oct;83(1):57-66. Pubmed
                        2. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed

                        4. Monocarboxylate transporter 1

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        Monocarboxylate transporter 1 P53985 Details

                        References:

                        1. Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. Pubmed

                        5. Solute carrier family 22 member 7

                        Kind: protein

                        Organism: Human

                        Pharmacological action: unknown

                        Actions: substrate

                        Components

                        Name UniProt ID Details
                        Solute carrier family 22 member 7 Q9Y694 Details

                        References:

                        1. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. Pubmed

                        Comments
                        Drug created on June 13, 2005 07:24 / Updated on October 03, 2013 14:46