Tìm theo
Valproic Acid
Các tên gọi khác (20 ) :
  • 2-n-propyl-n-valeric acid
  • 2-PROPYL-pentanoic acid
  • 2-Propylpentanoic Acid
  • 2-Propylvaleric Acid
  • 4-heptanecarboxylic acid
  • Acide valproique
  • Acido valproico
  • Acidum valproicum
  • Depakene
  • di-n-propylacetic acid
  • Di-N-propylessigsaeure
  • Di-n-propylessigsäure
  • Dipropylacetic acid
  • DPA
  • n-DPA
  • Valproate
  • VALPROIC acid
  • Valproinsaeure
  • Valproinsäure
  • VPA
Thuốc điều trị về tâm thần
Thuốc Gốc
Small Molecule
CAS: 99-66-1
ATC: N03AG01
ĐG : Abbott Laboratories Ltd. , http://www.abbott.com
CTHH: C8H16O2
PTK: 144.2114
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C8H16O2
Phân tử khối
144.2114
Monoisotopic mass
144.115029756
InChI
InChI=1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10)
InChI Key
InChIKey=NIJJYAXOARWZEE-UHFFFAOYSA-N
IUPAC Name
2-propylpentanoic acid
Traditional IUPAC Name
valproic acid
SMILES
CCCC(CCC)C(O)=O
Độ tan chảy
120-130 °C
Độ hòa tan
1.3 mg/mL
logP
2.75
logS
-1.86
pKa (strongest acidic)
5.14
PSA
37.3 Å2
Refractivity
40.25 m3·mol-1
Polarizability
17 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
-1
Number of Rings
0
Bioavailability
1
Rule of Five
true
pKa
4.8
Dược Lực Học : The 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.
Cơ Chế Tác Dụng : 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. Valproic 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.
Dược Động Học :
▧ Absorption :
Rapid 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 binding :
Concentration-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.
▧ Route of Elimination :
Valproate 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 Life :
9-16 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]
Độc Tính : Oral, 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.
Chỉ Định : For 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.
Tương Tác Thuốc :
  • Acetylsalicylic acid Acetylsalicylic acid increases the effect of valproic acid.
  • Asenapine Valproate completely inhibits the glucuronidation of asenapine but does not effect its exposure. Dose adjustment is not necessary with concomitant therapy.
  • Carbamazepine Decreases the effect of valproic acid
  • Clarithromycin The 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.
  • Eltrombopag Affects hepatic CYP2C9/10 metabolism, will increase effect/level of eltrombopag.
  • Erythromycin The 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.
  • Felbamate Felbamate, 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 Phenylbutyrate Valproic acid may induce hyperammonemia. Monitor ammonia levels closely when use of valproic acid is necessary in UCD patients.
  • Lacosamide Valproic 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.
  • Lamotrigine Valproic 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.
  • Lorazepam Valproic 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.
  • Nimodipine Valproic acid increases the effect of nimodipine
  • Rifampicin Rifampin 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.
  • Rufinamide Valproic 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.
  • Silodosin Strong UGT2B7 inhibitors may increase levels of silodosin. Monitor concomitant therapy closely.
  • Telithromycin The 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.
  • Tipranavir Tipranavir decreases the concentration of Valproic acid. Monitor Valproid acid efficacy.
  • Vigabatrin Vigabatrin reduces serum concentrations of valproic acid by 8%.
Liều Lượng & Cách Dùng : Capsule - Oral - 250 mg
Capsule, delayed release - Oral - 125 mg, 250 mg, 500 mg
Injection, solution - Intravenous - 100 mg/mL
Solution - Oral - 250 mg/5 mL
Syrup - Oral - 250 mg/mL
Tablet, delayed release - Oral - 125 mg, 250 mg, 500 mg
Tablet, extended release - Oral - 250 mg, 500 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Convulex
  • Công ty :
    Sản phẩm biệt dược : Depacon
  • Công ty :
    Sản phẩm biệt dược : Depakene
  • Công ty :
    Sản phẩm biệt dược : Depakine
  • Công ty :
    Sản phẩm biệt dược : Depakote
  • Công ty :
    Sản phẩm biệt dược : Depakote ER
  • Công ty :
    Sản phẩm biệt dược : Deprakine
  • Công ty :
    Sản phẩm biệt dược : Encorate
  • Công ty :
    Sản phẩm biệt dược : Epilim
  • Công ty :
    Sản phẩm biệt dược : Epival
  • Công ty :
    Sản phẩm biệt dược : Stavzor
  • Công ty :
    Sản phẩm biệt dược : Valcote
  • Công ty :
    Sản phẩm biệt dược : Valparin
  • Công ty :
    Sản phẩm biệt dược : Valproic
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00313
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3121
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505925
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07185
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00399
ChemSpider
http://www.chemspider.com/Chemical-Structure.3009.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0121-0675-16
PharmGKB
http://www.pharmgkb.org/drug/PA451846
Wikipedia
http://en.wikipedia.org/wiki/Valproic_Acid
RxList
http://www.rxlist.com/cgi/generic2/depakene.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dep1124.shtml
Drugs.com
http://www.drugs.com/cdi/valproate.html
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