Tìm theo
Clobazam
Các tên gọi khác (4 ) :
  • 1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepine
  • 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione
  • Clobazam
  • Clobazamum
Thuốc chống co giật, chống động kinh
Thuốc Gốc
Small Molecule
CAS: 22316-47-8
ATC: N05BA09
CTHH: C16H13ClN2O2
PTK: 300.74
Clobazam belongs to the 1,5-benzodiazepine class of drugs and is expected to have a better side-effect profile compared to older 1,4-benzodiazepines. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. The oral preparation was FDA approved on October 21, 2011. An oral suspension is expected to be available in 2013.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C16H13ClN2O2
Phân tử khối
300.74
Monoisotopic mass
300.066555377
InChI
InChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3
InChI Key
InChIKey=CXOXHMZGEKVPMT-UHFFFAOYSA-N
IUPAC Name
7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione
Traditional IUPAC Name
clobazam
SMILES
CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O
Độ tan chảy
180-182
Độ hòa tan
188 mg/L
logP
2.12
logS
-3.3
pKa (strongest acidic)
4.07
pKa (Strongest Basic)
-6.7
PSA
40.62 Å2
Refractivity
80.3 m3·mol-1
Polarizability
30.07 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
2
H Bond Donor Count
0
Physiological Charge
-1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Similar to other benzodiazepines, clobazam binds to the interface of the α and γ2-subunit of the GABA-A receptor. However, it is considered a partial agonist to GABA-A receptors which sets clobazam apart from 1,4-benzodiazepines which are full agonist. The significance of this difference is that one may experience less sedation with clobazam than with other benzodiazepines. Unlike the endogenous GABA ligand, clobazam binds allosterically to the GABA receptor to increase the frequency of the chloride channel opening and membrane permeability to chloride ions. Pharmacodynamic tolerance has been demonstrated in animal models.
Cơ Chế Tác Dụng : Clobazam belongs to the 1,5-benzodiazepine class of drugs and is expected to have a better side-effect profile compared to older 1,4-benzodiazepines. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. The oral preparation was FDA approved on October 21, 2011. An oral suspension is expected to be available in 2013. Clobazam binds at distinct binding sites associated with the chloride ionopore at the post-synaptic GABA receptor. These GABA receptors are in various locations in the CNS (limbic, reticular formation) and clobazam increases the duration of time for which the chloride ionopore is open. As a result, hyper polarization and stabilization of the membrane occur as the post-synaptic inhibitory effect of GABA is enhanced.
Dược Động Học :
▧ Absorption :
After oral administration of clobazam, it is almost completely absorbed (87% of dose). Bioavailability relative to solution was almost at 100%. Food does not affect absorption. Tmax = 1-3 hours.
▧ Volume of Distribution :
Vdss = 100 L. This high volume of distribution suggests extensive distribution to body tissues.
▧ Protein binding :
Clobazam is the primary circulating entity in the serum and is highly protein-bound (80-90%).
▧ Metabolism :
Clobazam is extensively metabolized in the liver via N-demethylation and hydroxylation. Clobazam has two major metabolites: N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, the former of which is active. Norclobazam is one-fourth the potency of clobazam. The main enzyme that facilitates the process of N-demethylation is CYP3A4, and to a lesser extent by CYP2C19 and CYP2B6. Norclobazam itself is also metabolized via hydroxylation, primarily by CYP2C19. The formation of 4'-hydroxyclobazam is facilitated by CYP2C18 and CYP2C19. A factor in determining extent of metabolism is the genetic profile of the individual patient as CYP2C19 is a polymorphic enzyme.
▧ Route of Elimination :
Clobazam is eliminated via the urine (~94%) as metabolites.
▧ Half Life :
The mean elimination half life of an oral dose of clobazam 40 mg is 32 hours. It's main metabolite, norclobazam, as a half life of 57 hours. The half life in adult patients with epilepsy are higher than those that are healthy.
▧ Clearance :
Median estimated clearance = 2.49 L/h
Độc Tính : The most common adverse effects include somnolence, pyrexia, upper respiratory tract infection, and lethargy.
Chỉ Định : For treatment and management of epilepsy and seizures associated with Lennox-Gastaut syndrome, a difficult-to-treat form of childhood epilepsy.
Tương Tác Thuốc :
  • Axitinib Clobazam decreases levels by affecting CYP3A4 metabolism. Consider alternate therapy.
  • Clozapine Increased risk of toxicity
  • Kava Kava may increase the effect of the benzodiazepine, clobazam.
  • Ketoconazole Clobazam may increase levels by affecting CYP2C19 metabolism. Interaction is significant so monitor closely. Dose adjustment may be necessary.
  • Midazolam Clobazam decrease the Cmax and AUC of midazolam by approximately 25% of both and increases the Cmax and AUC of its metabolite. Dose adjustment is not necessary.
  • Rotigotine Concomitant therapy may potentiate adverse CNS effects such as increased sedation or respiratory depression. Monitor therapy closely.
  • Telithromycin Telithromycin may reduce clearance of Clobazam. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Clobazam if Telithromycin is initiated, discontinued or dose changed.
  • Ticlopidine Ticlopidine may decrease the metabolism and clearance of Clobazam. Consider alternate therapy or monitor for adverse/toxic effects of Clobazam if Ticlopidine is initiated, discontinued or dose changed.
  • Tipranavir Tipranavir may decrease the metabolism and clearance of Clobazam. Consider alternate therapy or monitor for Clobazam toxic effects if Tipranavir is initiated or dose increased.
  • Triprolidine The CNS depressants, Triprolidine and Clobazam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Voriconazole Voriconazole may increase the serum concentration of clobazam by decreasing its metabolism. Monitor for clobazam toxicity if voriconazole is initiated or dose increased.
Liều Lượng & Cách Dùng : Suspension - Oral - 2.5 mg/mL
Tablet - Oral - 5 mg, 10 mg, 20 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Aedon
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Castilium
  • Công ty : Square
    Sản phẩm biệt dược : Clobam
  • Công ty : Sherfarma
    Sản phẩm biệt dược : Clobamax
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Frisium
  • Công ty : Chile
    Sản phẩm biệt dược : Grifoclobam
  • Sản phẩm biệt dược : Mystan
  • Công ty : Sanofi Aventis
    Sản phẩm biệt dược : Noiafren
  • Công ty : Lundbeck
    Sản phẩm biệt dược : Onfi
  • Công ty :
    Sản phẩm biệt dược : Sederlona
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Urbanil
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Urbanol
  • Công ty : Sanofi-Aventis
    Sản phẩm biệt dược : Urbanyl
  • Công ty : Hudson
    Sản phẩm biệt dược : Venium
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00349
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2789
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506115
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01253
ChemSpider
http://www.chemspider.com/Chemical-Structure.2687.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/67386-313-21
PharmGKB
http://www.pharmgkb.org/drug/PA10888
Wikipedia
http://en.wikipedia.org/wiki/Clobazam
RxList
http://www.rxlist.com/onfi-drug.htm
Drugs.com
http://www.drugs.com/cdi/clobazam.html
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