Tìm theo
Isoniazid
Các tên gọi khác (10 ) :
  • 4-pyridinecarbohydrazide
  • INH
  • Isoniazid
  • Isonicotinic acid hydrazide
  • Isonicotinic hydrazide
  • Isonicotinohydrazide
  • Isonicotinoylhydrazide
  • Isonicotinsaeurehydrazid
  • Isonicotinylhydrazine
  • Pyridine-4-carboxylic acid hydrazide
Thuốc trị ký sinh trùng, chống nhiễm khuẩn
Thuốc Gốc
Small Molecule
CAS: 54-85-3
ATC: J04AC01
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C6H7N3O
PTK: 137.1393
Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C6H7N3O
Phân tử khối
137.1393
Monoisotopic mass
137.058911861
InChI
InChI=1S/C6H7N3O/c7-9-6(10)5-1-3-8-4-2-5/h1-4H,7H2,(H,9,10)
InChI Key
InChIKey=QRXWMOHMRWLFEY-UHFFFAOYSA-N
IUPAC Name
pyridine-4-carbohydrazide
Traditional IUPAC Name
isoniazid
SMILES
NNC(=O)C1=CC=NC=C1
Độ tan chảy
171.4 °C
Độ hòa tan
1.4E+005 mg/L (at 25 °C)
logP
-0.70
logS
0.01
pKa (strongest acidic)
13.61
pKa (Strongest Basic)
3.35
PSA
68.01 Å2
Refractivity
37.46 m3·mol-1
Polarizability
13.21 Å3
Rotatable Bond Count
1
H Bond Acceptor Count
3
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
1
Bioavailability
1
Rule of Five
true
pKa
1.82 (at 20 °C)
Dược Lực Học : Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.
Cơ Chế Tác Dụng : Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [PubChem] Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
Dược Động Học :
▧ Absorption :
Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.
▧ Protein binding :
Very low (0-10%)
▧ Metabolism :
Primarily hepatic. Isoniazid is acetylated by N -acetyl transferase to N -acetylisoniazid; it is then biotransformed to isonicotinic acid and monoacetylhydrazine. Monoacetylhydrazine is associated with hepatotoxicity via formation of a reactive intermediate metabolite when N-hydroxylated by the cytochrome P450 mixed oxidase system. The rate of acetylation is genetically determined. Slow acetylators are characterized by a relative lack of hepatic N -acetyltransferase.
▧ Route of Elimination :
From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours.
▧ Half Life :
Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.
Độc Tính : LD50 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.
Chỉ Định : For the treatment of all forms of tuberculosis in which organisms are susceptible.
Tương Tác Thuốc :
  • Acenocoumarol Isoniazid may increase the anticoagulant effect of acenocoumarol.
  • Acetaminophen Risk of hepatotoxicity
  • Aminophylline Isoniazid may increase the effect and toxicity of oxtriphylline.
  • Anisindione Isoniazid may increase the anticoagulant effect of anisindione.
  • Bromazepam Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if isoniazid is initiated, discontinued or dose changed. Dosage adjustments may be required.
  • Carbamazepine Carbamazepine effect is increased as is isoniazid toxicity
  • Carisoprodol Strong CYP2C19 inhibitors such as isoniazid may decrease the metabolism of CYP2C19 substrates such as carisoprodol. Consider an alternative for one of the interacting drugs in order to avoid toxicity of the substrate. Some combinations are specifically contraindicated by manufacturers. Suggested dosage adjustments are also offered by some manufacturers. Please review applicable package inserts. Monitor for increased effects of the CYP substrate if a CYP inhibitor is initiated/dose increased, and decreased effects if a CYP inhibitor is discontinued/dose decreased.
  • Dantrolene Isoniazid may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if isoniazid is initiated, discontinued or dose changed.
  • Dicoumarol Isoniazid may increase the anticoagulant effect of dicumarol.
  • Disulfiram Increased risk of CNS adverse effects
  • Dyphylline Increases the effect and toxicity of theophylline
  • Eltrombopag Affects hepatic CYP1A2 metabolism, increases Eltrombopag level or affect.
  • Ethotoin Isoniazid increases the effect of phenytoin in 20% of patients
  • Fosphenytoin Isoniazid may increase the effect of phenytoin in 20% of patients.
  • Ketoconazole Isoniazid decreases the effect of ketoconazole
  • Mephenytoin Isoniazid increases the effect of phenytoin in 20% of patients
  • Oxtriphylline Isoniazid may increase the effect and toxicity of oxtriphylline.
  • Pethidine Possible episodes of hypotension
  • Phenytoin Isoniazid increases the effect of phenytoin in 20% of patients
  • Tacrolimus The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Isoniazid is initiated, discontinued or dose changed.
  • Tadalafil Isoniazid may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
  • Tamoxifen Isoniazid may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Isoniazid may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Isoniazid is initiated, discontinued or dose changed.
  • Tamsulosin Isoniazid, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Isoniazid is initiated, discontinued, or dose changed.
  • Telithromycin Isoniazid may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects.
  • Temsirolimus Isoniazid may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
  • Teniposide The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Isoniazid is initiated, discontinued or dose changed.
  • Theophylline Isoniazid may increase the therapeutic and adverse effects of theophylline.
  • Tiagabine The strong CYP3A4 inhibitor, Isoniazid, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Isoniazid is initiated, discontinued or dose changed.
  • Tolterodine Isoniazid may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Tramadol Isoniazid may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Isoniazid may decrease the effect of Tramadol by decreasing active metabolite production.
  • Trazodone The CYP3A4 inhibitor, Isoniazid, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Isoniazid is initiated, discontinued or dose changed.
  • Trimipramine The strong CYP3A4/CYP2C19 inhibitor, Isoniazide, may decrease the metabolism and clearance of Trimipramine, a CYP3A4/CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Isoniazid is initiated, discontinued or dose changed.
  • Vardenafil Isoniazid, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
  • Venlafaxine Isoniazid, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Isoniazid is initiated, discontinued, or dose changed.
  • Verapamil Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Isoniazid is initiated, discontinued or dose changed.
  • Vinblastine Isoniazid, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Isoniazid is initiated, discontinued or dose changed.
  • Vincristine Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Isoniazid is initiated, discontinued or dose changed.
  • Vinorelbine Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Isoniazid is initiated, discontinued or dose changed.
  • Warfarin Isoniazid may increase the anticoagulant effect of warfarin.
  • Zolpidem Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if isoniazid is initiated, discontinued or dose changed.
  • Zonisamide Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if isoniazid is initiated, discontinued or dose changed.
  • Zopiclone Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if isoniazid is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Powder - Oral
Syrup - Oral
Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Piam
    Sản phẩm biệt dược : Nicozid
  • Công ty : Zentiva
    Sản phẩm biệt dược : Nidrazid
  • Công ty : Sandoz
    Sản phẩm biệt dược : Nydrazid
  • Công ty : Sopharma
    Sản phẩm biệt dược : Rimicid
  • Công ty : Roche
    Sản phẩm biệt dược : Rimifon
  • Công ty : Novartis
    Sản phẩm biệt dược : Servizid
  • Công ty : Meda
    Sản phẩm biệt dược : Tibinide
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00951
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3767
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506039
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07054
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00346
ChemSpider
http://www.chemspider.com/Chemical-Structure.3635.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0555-0066-02
PharmGKB
http://www.pharmgkb.org/drug/PA450112
Wikipedia
http://en.wikipedia.org/wiki/Isoniazid
RxList
http://www.rxlist.com/cgi/generic2/isoniaz.htm
Drugs.com
http://www.drugs.com/cdi/isoniazid.html
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