Tìm theo
Vigabatrin
Các tên gọi khác (8 ) :
  • 4-Amino-5-hexenoic acid
  • gamma-Vinyl GABA
  • gamma-Vinyl-gamma-aminobutyric acid
  • GVG
  • Vigabatrin
  • Vigabatrina
  • Vigabatrine
  • Vigabatrinum
enzyme inhibitors, anticonvulsants, gaba agents
Thuốc Gốc
Small Molecule
CAS: 60643-86-9
ATC: N03AG04
ĐG : Lundbeck Inc. , http://www.lundbeckinc.com
CTHH: C6H11NO2
PTK: 129.157
An analogue of gamma-aminobutyric acid, vigabatrin is an irreversible inhibitor of 4-aminobutyrate transaminase, the enzyme responsible for the catabolism of gamma-aminobutyric acid. (From Martindale The Extra Pharmacopoeia, 31st ed). Off-label uses include treatment of cocaine dependence.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C6H11NO2
Phân tử khối
129.157
Monoisotopic mass
129.078978601
InChI
InChI=1S/C6H11NO2/c1-2-5(7)3-4-6(8)9/h2,5H,1,3-4,7H2,(H,8,9)
InChI Key
InChIKey=PJDFLNIOAUIZSL-UHFFFAOYSA-N
IUPAC Name
4-aminohex-5-enoic acid
Traditional IUPAC Name
vigabatrin
SMILES
NC(CCC(O)=O)C=C
Độ hòa tan
55.1 mg/mL
logP
-2.16
logS
-0.13
pKa (strongest acidic)
4.61
pKa (Strongest Basic)
9.91
PSA
63.32 Å2
Refractivity
34.29 m3·mol-1
Polarizability
13.64 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
3
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
0
Bioavailability
1
Rule of Five
true
Dược Lực Học : Vigabatrin is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin prevents the catabolism of GABA by irreversibly inhibiting the enzyme GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. However, vigabatrin is not a potent inhibitor of GABA-T with a Ki of 10 mM.
Cơ Chế Tác Dụng : An analogue of gamma-aminobutyric acid, vigabatrin is an irreversible inhibitor of 4-aminobutyrate transaminase, the enzyme responsible for the catabolism of gamma-aminobutyric acid. (From Martindale The Extra Pharmacopoeia, 31st ed). Off-label uses include treatment of cocaine dependence. Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active.
Dược Động Học :
▧ Absorption :
Rapidly absorbed following oral administration, absorption is comparable between neonates, infants, and children. Cmax, 50 mg/kg dose, neonates= 14 mg/L; Tmax, 50 mg/kg dose, neonates = 2.1 hours; However, extent of absorption is higher and elimination half life is longer in neonates compared to children and infants. This is because neonates have reduced renal function compared to the aforementioned population groups. AUC, 50 mg/kg dose, neonates = 142.6 ± 44.0 mg/L/hr; Food may slightly decrease the rate (Cmax decreased by 33%, Tmax increased to 2 hours), but not the extent of absorption. Furthermore, vigabatrin does not cross the blood-brain-barrier well, thus high doses are needed.
▧ Volume of Distribution :
1.1 L/kg
▧ Protein binding :
Not protein bound
▧ Metabolism :
Almost no metabolic transformation. Does not induce the hepatic cytochrome P450 system.
▧ Route of Elimination :
Eliminated primarily through renal excretion as unchanged drugs (80%).
▧ Half Life :
Neonates, 50 mg/kg = 7.5 ± 2.1 hours (due to reduced renal function); Infants = 5.7 hours; Adults = 7.5 hours; Elderly = 12 - 13 hours
▧ Clearance :
Infants = 2.4 ± 0.8 L/h; Children = 5.7 ± 2.5 L/h
Độc Tính : LD50, oral, rat: 3000 mg/kg; Visual field defects may occur following cumulative doses in excess of 2 kg.
Chỉ Định : For use as an adjunct in treatment resistant epilepsy, refractory complex partial seizures, and secondary generalized seizures. It is also used as monotherapy in infantile spasms in West syndrome.
Tương Tác Thuốc :
  • Clonazepam Vigabatrin increases Cmax of clonazepam by 30% and decreases Tmax by 45%
  • Fosphenytoin Vigabatrin decreases the effect of hydantoin
  • Mefloquine Mefloquine may decrease the serum concentration of Vigabatrin. This may increase the risk of seizure in patients receiving Vigabatrin to prevent seizures. Consider alternate therapy or monitor for changes in Vigabatrin serum concentration, therapeutic or adverse effects if Mefloquin is initiated, discontinued or dose changed.
  • Methotrimeprazine Additive CNS depression may occur. Dose adjustments may be required if one agent is added to existing therapy with the other agent. Monitor for increased CNS depression during concomitant therapy.
  • Phenobarbital Vigabatrin reduces serum concentrations of phenobarbital by 8-16%.
  • Phenytoin Vigabatrin reduces plasma levels of phenytoin by 16-20% which may be due to induction of CYP2C. Consider dosage adjustment.
  • Sildenafil Increased anticonvulsant effects of vigabatrin due to pharmacodynamic synergism. Monitor for adverse effects during concomitant therapy.
  • Triprolidine The CNS depressants, Triprolidine and Vigabatrin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Valproic Acid Vigabatrin reduces serum concentrations of valproic acid by 8%.
Liều Lượng & Cách Dùng : Powder, for solution - Oral - 500 mg/packet
Powder, for suspension - Oral - 0.5 g/sachet
Tablet - Oral - 500 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01080
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5665
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507052
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07500
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00535
ChemSpider
http://www.chemspider.com/Chemical-Structure.5463.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50118886
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/67386-211-65
PharmGKB
http://www.pharmgkb.org/drug/PA10231
Wikipedia
http://en.wikipedia.org/wiki/Vigabatrin
RxList
http://www.rxlist.com/sabril-drug.htm
Drugs.com
http://www.drugs.com/cdi/vigabatrin.html
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