Tìm theo
Midazolam
Các tên gọi khác (4 ) :
  • Buccolam
  • Dormicum
  • Midazolam
  • Midazolamum
Thuốc điều trị về tâm thần
Thuốc Gốc
Small Molecule
CAS: 59467-70-8
ATC: N05CD08
ĐG : Akorn Inc. , http://www.akorn.com
CTHH: C18H13ClFN3
PTK: 325.767
A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [PubChem] Midazolam is a schedule IV drug in the United States.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H13ClFN3
Phân tử khối
325.767
Monoisotopic mass
325.078203343
InChI
InChI=1S/C18H13ClFN3/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13/h2-9H,10H2,1H3
InChI Key
InChIKey=DDLIGBOFAVUZHB-UHFFFAOYSA-N
IUPAC Name
12-chloro-9-(2-fluorophenyl)-3-methyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene
Traditional IUPAC Name
midazolam
SMILES
CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12
Độ tan chảy
159 °C
Độ hòa tan
0.024 mg/mL
logP
3.33
logS
-4.5
pKa (Strongest Basic)
6.57
PSA
30.18 Å2
Refractivity
99.43 m3·mol-1
Polarizability
32.7 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
2
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. Pharmacodynamic properties of midazolam and its metabolites, which are similar to those of other benzodiazepines, include sedative, anxiolytic, amnesic and hypnotic activities. Benzodiazepine pharmacologic effects appear to result from reversible interactions with the (gamma)-amino butyric acid (GABA) benzodiazepine receptor in the CNS, the major inhibitory neurotransmitter in the central nervous system. The action of midazolam is readily reversed by the benzodiazepine receptor antagonist, flumazenil.
Cơ Chế Tác Dụng : A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [PubChem] Midazolam is a schedule IV drug in the United States. It is thought that the actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the brain. Benzodiazepines increase the activity of GABA, thereby producing a calming effect, relaxing skeletal muscles, and inducing sleep. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening.
Dược Động Học :
▧ Absorption :
Rapidly absorbed after oral administration. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36%. The absolute bioavailability, if given intramuscularly (IM), is greater than 90%. Cmax, IM = 90 ng/mL; Tmax, IM = 0.5 hours. Following IM administered, Cmax for midazolam and its 1-hydroxy metabolite were approxiately one-half of those achieved after intravenous injection.
▧ Volume of Distribution :
* 1.24 to 2.02 L/kg [pediatric patients (6 months to <16 years) receiving 0.15 mg/kg IV midazolam,] * 1 to 3.1 L/kg [intravenously administered, healthy adults] Female gender, old age, and obesity may increase the volume of distribution. Midazolam may also cross the placenta and has been detected in human milk and cerebrospinal fluid.
▧ Protein binding :
97% protein bound.
▧ Metabolism :
Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, (alpha)-hydroxymidazolam (also known as 1-hydroxy-midazolam), and 4-hydroxymidazolam (makes up 5% or less of the biotransformation products). 1-hydroxy-midazolam is at least as potent as the parent compound and may contributed to the overall activity of midazolam. In vitro studies have demonstrated that the affinities of 1- and 4-hydroxy-midazolam for the benzodiazepine receptor are approximately 20% and 7%, respectively, relative to midazolam. It also undergoes N-glucuronidation via UGT1A4.
▧ Route of Elimination :
Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, α-hydroxymidazolam, followed by glucuronidation of the α–hydroxyl metabolite which is present in unconjugated and conjugated forms in human plasma. The α- hydroxymidazolam glucuronide is then excreted in urine. No significant amount of parent drug or metabolites is extractable from urine before beta-glucuronidase and sulfatase deconjugation, indicating that the urinary metabolites are excreted mainly as conjugates. The amount of midazolam excreted unchanged in the urine when given intravenously is less than 0.5%. 45% to 57% of the dose was excreted in the urine as 1-hydroxymethyl midazolam conjugate.
▧ Half Life :
Intravenous, healthy adults = 1.8 to 6.4 hours (mean of 3 hours)
▧ Clearance :
* 9.3 to 11 mL/min/kg [pediatric patients (6 months to <16 years old)] * 0.25 to 0.54 L/hr/kg [intravenous, healthy adults]
Độc Tính : LD50=825 mg/kg (Orally in rats). Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs.
Chỉ Định : The midazolam injection is indicated for preoperative sedation/anziolysis/amnesia. It is also an agent for sedation/anziolysis/amnesia prior to or during diagnostic, therapeutic, or endoscopic procedures. Midazolam can also be given intravenously for induction of general anaesthesia.
Tương Tác Thuốc :
  • Amprenavir Amprenavir may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Aprepitant Aprepitant may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Atazanavir Atazanavir may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • BXT-51072 BXT-51072 weakly inhibits midazolam clearance.
  • Carbamazepine Carbamazepine may decrease the effect of the benzodiazepine, midazolam.
  • Cimetidine Cimetidine may increase the effect of the benzodiazepine, midazolam.
  • Clarithromycin The macrolide, clarithromycin, may increase the effect of the benzodiazepine, midazolam.
  • Clobazam 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.
  • Clozapine Increased risk of toxicity
  • Crizotinib Strong CYP3A4 inhibitors may increase levels of crizotinib. Monitor concomitant therapy closely.
  • Crizotinib Strong CYP3A4 inhibitors may increase levels of crizotinib. Monitor concomitant therapy closely.
  • Dabrafenib Dabrafenib decreased the maximum concentration (Cmax) and area under the curve (AUC) of midazolam (a substrate of CYP3A4) by 61% and 74%, respectively.
  • Delavirdine The antiviral agent, delavirdine, may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Diltiazem The calcium channel blocker, diltiazem, may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Docetaxel Midazolam may increase the serum levels and toxicity of docetaxel.
  • Efavirenz The antiviral agent, efavirenz, may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Erythromycin The macrolide, erythromycin, may increase the effect of the benzodiazepine, midazolam.
  • Ethotoin Ethotoin may increase the metabolism of midazolam via CYP3A4.
  • Fluconazole Fluconazole may increase the effect of the benzodiazepine, midazolam.
  • Fosamprenavir Fosamprenavir may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Fosphenytoin Fosphenytoin may increase the metabolism of midazolam via CYP3A4.
  • Indinavir The protease inhibitor, indinavir, may increase the effect of the benzodiazepine, midazolam.
  • Itraconazole Itraconazole may increase the effect of the benzodiazepine, midazolam.
  • Josamycin The macrolide, josamycin, may increase the effect of the benzodiazepine, midazolam.
  • Kava Kava may increase the effect of the benzodiazepine, midazolam.
  • Ketoconazole Ketoconazole may increase the effect of the benzodiazepine, midazolam.
  • Mephenytoin Mephenytoin may increase the metabolism of midazolam via CYP3A4.
  • Nelfinavir The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, midazolam.
  • Omeprazole Omeprazole may increase the effect of the benzodiazepine, midazolam.
  • Phenytoin Phenytoin may increase the metabolism of midazolam via CYP3A4.
  • Quinupristin This combination presents an increased risk of toxicity
  • Rifampicin Rifampin may increase the metabolism of midazolam. Monitor for changes in the therapeutic and adverse effects of midazolam if rifampin is initiated, discontinued or dose changed.
  • Ritonavir The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, midazolam.
  • Saquinavir The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, midazolam.
  • St. John's Wort St. John's Wort may decrease the effect of the benzodiazepine, midazolam.
  • Telaprevir Telaprevir increases AUC and Cmax of oral midazolam by approximately 9-fold and 3-fold respectively.
  • Telithromycin Telithromycin may increase the effect and toxicity of the benzodiazepine, midazolam.
  • Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Midazolam. Concomitant therapy is contraindicated.
  • Triprolidine The CNS depressants, Triprolidine and Midazolam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Vemurafenib Vemurafenib decreases the AUC (CYP3A4 substrate) by 39%.
  • Verapamil Verapamil may increase the serum concentration of Midazolam by decreasing its metabolism. Avoid concomitant therapy if possible or consider a dose reduction in the initial dose of Midazolam.
  • Voriconazole Voriconazole may increase the serum concentration of midazolam by decreasing its metabolism. Monitor for midazolam toxicity if voriconazole is initiated or dose increased.
Liều Lượng & Cách Dùng : Injection, solution - Parenteral
Syrup - Oral - 2 mg/mL
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : General Pharma
    Sản phẩm biệt dược : Anquil
  • Công ty : Pharmaceutical
    Sản phẩm biệt dược : Benzosed
  • Công ty : Richmond
    Sản phẩm biệt dược : Dalam
  • Công ty : Specifar
    Sản phẩm biệt dược : Damizol
  • Công ty : Dem Ilaç
    Sản phẩm biệt dược : Demizolam
  • Công ty : Roche
    Sản phẩm biệt dược : Doricum
  • Công ty : Roche
    Sản phẩm biệt dược : Dormicum
  • Công ty : Scott
    Sản phẩm biệt dược : Dormid
  • Công ty : Chalver
    Sản phẩm biệt dược : Dormipron
  • Công ty : Cristália
    Sản phẩm biệt dược : Dormire
  • Công ty : Square
    Sản phẩm biệt dược : Dormitol
  • Công ty : Demo
    Sản phẩm biệt dược : Dormixal
  • Công ty : Roche
    Sản phẩm biệt dược : Dormonid
  • Công ty : Northia
    Sản phẩm biệt dược : Drimnorth
  • Công ty : IFET
    Sản phẩm biệt dược : Epistatus
  • Công ty : Galenika
    Sản phẩm biệt dược : Flormidal
  • Công ty : Ranbaxy
    Sản phẩm biệt dược : Fulsed
  • Công ty : Terapia
    Sản phẩm biệt dược : Fulsed Injection
  • Công ty : Bio-Pharma
    Sản phẩm biệt dược : Garen
  • Công ty : Gobbi
    Sản phẩm biệt dược : Gobbizolam
  • Công ty : EMS
    Sản phẩm biệt dược : Hipnazolam
  • Công ty : Pharos
    Sản phẩm biệt dược : Hipnoz
  • Công ty : Incepta
    Sản phẩm biệt dược : Hypnofast
  • Công ty : Roche
    Sản phẩm biệt dược : Hypnovel
  • Công ty : Roche
    Sản phẩm biệt dược : Ipnovel
  • Công ty : Lafi
    Sản phẩm biệt dược : Nocturna
  • Công ty : Rimsa
    Sản phẩm biệt dược : Setam
  • Công ty : Fisiopharma
    Sản phẩm biệt dược : Talentum
  • Công ty : Sanitas
    Sản phẩm biệt dược : Terap
  • Công ty : Roche
    Sản phẩm biệt dược : Versed
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00683
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=4192
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507611
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07524
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00550
ChemSpider
http://www.chemspider.com/Chemical-Structure.4047.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=21363
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0574-0150-04
PharmGKB
http://www.pharmgkb.org/drug/PA450496
Wikipedia
http://en.wikipedia.org/wiki/Midazolam
RxList
http://www.rxlist.com/cgi/generic2/versedsyr.htm
Drugs.com
http://www.drugs.com/cdi/midazolam.html
... loading
... loading