Tìm theo
Abacavir
Các tên gọi khác (3) :
  • {(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol
  • Abacavir
  • ABC
Thuốc trị ký sinh trùng, chống nhiễm khuẩn
Thuốc Gốc
Small Molecule
CAS: 136470-78-5
ATC: J05AF06
ĐG : A-S Medication Solutions LLC , http://orders.a-smeds.com
CTHH: C14H18N6O
PTK: 286.3323
Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. [Wikipedia] Chemically, it is a synthetic carbocyclic nucleoside and is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. In vivo, abacavir sulfate dissociates to its free base, abacavir.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H18N6O
Phân tử khối
286.3323
Monoisotopic mass
286.154209228
InChI
InChI=1S/C14H18N6O/c15-14-18-12(17-9-2-3-9)11-13(19-14)20(7-16-11)10-4-1-8(5-10)6-21/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19)/t8-,10+/m1/s1
InChI Key
InChIKey=MCGSCOLBFJQGHM-SCZZXKLOSA-N
IUPAC Name
[(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl]methanol
Traditional IUPAC Name
abacavir
SMILES
NC1=NC2=C(N=CN2[C@@H]2C[C@H](CO)C=C2)C(NC2CC2)=N1
Độ tan chảy
165 °C
Độ hòa tan
77 mg/mL (sulfate salt)
logP
1.20
logS
-2.4
pKa (strongest acidic)
15.41
pKa (Strongest Basic)
5.77
PSA
101.88 Å2
Refractivity
82.62 m3·mol-1
Polarizability
30.43 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
6
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The concentration of drug necessary to effect viral replication by 50 percent (EC50) ranged from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) and 0.07 to 1.0 μM against HIV-1IIIB and HIV-1BaL, respectively, and was 0.26 ± 0.18 μM against 8 clinical isolates. Abacavir had synergistic activity in cell culture in combination with the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, and the protease inhibitor (PI) amprenavir; and additive activity in combination with the NRTIs didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine.
Cơ Chế Tác Dụng : Abacavir (ABC) is a powerful nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. [Wikipedia] Chemically, it is a synthetic carbocyclic nucleoside and is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. In vivo, abacavir sulfate dissociates to its free base, abacavir. Abacavir is a carbocyclic synthetic nucleoside analogue and an antiviral agent. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analogue of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Viral DNA growth is terminated because the incorporated nucleotide lacks a 3'-OH group, which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation.
Dược Động Học :
▧ Absorption :
Rapid and extensive after oral administration (83% bioavailability, tablet). When a 300 mg tablet is given twice daily to subjects, the peak plasma concentration (Cmax) was 3.0 ± 0.89 mcg/mL and the area under the curve (AUC 0-12 hours) was 6.02 ± 1.73 mcg•hr/mL.
▧ Volume of Distribution :
* 0.86 ± 0.15 L/kg [IV administration]
▧ Protein binding :
Moderate (approximately 50%). Binding of abacavir to plasma protein was independent of concentration.
▧ Metabolism :
Hepatic, by alcohol dehydrogenase and glucuronosyltransferase to a 5′-carboxylic acid metabolite and 5′-glucuronide metabolite, respectively. These metabolites have no antiviral activity. Abacavir is not significantly metabolized by cytochrome P450 enzymes.
▧ Route of Elimination :
Elimination of abacavir was quantified in a mass balance study following administration of a 600-mg dose of 14C-abacavir: 99% of the radioactivity was recovered, 1.2% was excreted in the urine as abacavir, 30% as the 5′-carboxylic acid metabolite, 36% as the 5′-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal elimination accounted for 16% of the dose. Renal excretion of unchanged abacavir is a minor route of elimination in humans.
▧ Half Life :
1.54 ± 0.63 hours
▧ Clearance :
* 0.80 ± 0.24 L/hr/kg [asymptomatic, HIV-1-infected adult patients receiving single (IV dose of 150 mg]
Độc Tính : Some myocardial degeneration has been noticed in rats and mice. The most commonly reported adverse reactions of at least moderate intensity (incidence ≥10%) in adult HIV-1 clinical trials were nausea, headache, malaise and fatigue, nausea and vomiting, and dreams/sleep disorders. Serious hypersensitivity reactions have been associated with abacavir which has been strongly linked to the presence of the HLA-B*57:01 allele. This reaction manifests itself in patients within the first 6 weeks of treatment. Patients should be tested for the presence of this allele as recommended by the U.S Food and Drug Administration (FDA).
Chỉ Định : For the treatment of HIV-1 infection, in combination with other antiretroviral agents.
Tương Tác Thuốc :
  • Amprenavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Amprenavir. The antiviral response should be closely monitored.
  • Atazanavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Atazanavir. The antiviral response should be closely monitored.
  • Darunavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Darunavir. The antiviral response should be closely monitored.
  • Ethanol Abacavir is partly metabolized through the alcohol dehydrogenase enzyme system. Alcohol increases the area under the curve (about 41%) of Abacavir. Interaction does not appear to be clinically significant.
  • Fosamprenavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Fosamprenavir. The antiviral response should be closely monitored.
  • Ganciclovir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Ganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is required.
  • Indinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Indinavir. The antiviral response should be closely monitored.
  • Lopinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Lopinavir. The antiviral response should be closely monitored.
  • Nelfinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Nelfinavir. The antiviral response should be closely monitored.
  • Ribavirin Ribavirin may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.
  • Ribavirin Monophosphate Ribavirin Monophosphate may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.
  • Ritonavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Ritonavir. The antiviral response should be closely monitored.
  • Saquinavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Saquinavir. The antiviral response should be closely monitored.
  • Tipranavir The serum concentration of Abacavir may be decreased by protease inhibitors such as Tipranavir. The antiviral response should be closely monitored.
  • Valganciclovir The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.
Liều Lượng & Cách Dùng : Solution - Oral - 20 mg/mL
Tablet - Oral - 300 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Ziagen 300 mg tablet
    Giá bán buôn : USD >10.46
    Đơn vị tính : tablet
  • Biệt dược thương mại : Epzicom tablet
    Giá bán buôn : USD >35.78
    Đơn vị tính : tablet
  • Biệt dược thương mại : Ziagen 20 mg/ml Solution
    Giá bán buôn : USD >0.7
    Đơn vị tính : ml
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01048
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=441300
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505718
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07624
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D07057
ChemSpider
http://www.chemspider.com/Chemical-Structure.58649.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0661-01
PharmGKB
http://www.pharmgkb.org/drug/PA448004
Wikipedia
http://en.wikipedia.org/wiki/Abacavir
RxList
http://www.rxlist.com/cgi/generic/abavir.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1527.shtml
Drugs.com
http://www.drugs.com/cdi/abacavir.html
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