Tìm theo
Iloperidone
Các tên gọi khác (8 ) :
  • 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone
  • 4'-(3-(4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidino)propoxy)-3'-methoxyacetophenone
  • Fanapt
  • Fanapta
  • HP 873
  • Iloperidona
  • Iloperidonum
  • Zomaril
Thuốc Gốc
Small Molecule
CAS: 133454-47-4
ATC: N05AX14
CTHH: C24H27FN2O4
PTK: 426.4806
Iloperidone is an atypical antipsychotic for the treatment of schizophrenia symptoms. Hoechst Marion Roussel Inc. made initial inquiries into the drug; however, in May 1996, they discontinued research, and in June 1997 gave research rights to Titan Pharmaceuticals. Titan then handed over worldwide development, manufacturing and marketing rights to Novartis in August 1998. On June 9, 2004, Titan Pharmaceuticals announced that the Phase III development rights have been acquired by Vanda Pharmaceuticals. FDA approved on May 9, 2009.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C24H27FN2O4
Phân tử khối
426.4806
Monoisotopic mass
426.195485567
InChI
InChI=1S/C24H27FN2O4/c1-16(28)18-4-7-21(23(14-18)29-2)30-13-3-10-27-11-8-17(9-12-27)24-20-6-5-19(25)15-22(20)31-26-24/h4-7,14-15,17H,3,8-13H2,1-2H3
InChI Key
InChIKey=XMXHEBAFVSFQEX-UHFFFAOYSA-N
IUPAC Name
1-(4-{3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy}-3-methoxyphenyl)ethan-1-one
Traditional IUPAC Name
iloperidone
SMILES
COC1=C(OCCCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C=CC(=C1)C(C)=O
Độ hòa tan
Insoluble
logP
3.22
logS
-4.2
pKa (strongest acidic)
16.14
pKa (Strongest Basic)
7.91
PSA
64.8 Å2
Refractivity
116.65 m3·mol-1
Polarizability
46.51 Å3
Rotatable Bond Count
8
H Bond Acceptor Count
5
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors.
Cơ Chế Tác Dụng : Iloperidone is an atypical antipsychotic for the treatment of schizophrenia symptoms. Hoechst Marion Roussel Inc. made initial inquiries into the drug; however, in May 1996, they discontinued research, and in June 1997 gave research rights to Titan Pharmaceuticals. Titan then handed over worldwide development, manufacturing and marketing rights to Novartis in August 1998. On June 9, 2004, Titan Pharmaceuticals announced that the Phase III development rights have been acquired by Vanda Pharmaceuticals. FDA approved on May 9, 2009. Iloperidone is a dopamine D2 and 5-HT2A receptor antagonist and acts as a neuroleptic agent.
Dược Động Học :
▧ Absorption :
Well absorbed from the GI tract and Cmax is reached within 2-4 hours. Steady-state concentration is achieved in 3-4 days post-administration of iloperidone. Relative bioavailability of the tablet formulation compared to oral solution is 96%. Accumulation occurs in a predictable fashion.
▧ Volume of Distribution :
Apparent Vd = 1340-2800 L
▧ Protein binding :
95% of iloperidone is bound to protein. Percent bound is not altered by renal or hepatic impairment or combination therapy with ketoconazole.
▧ Metabolism :
Iloperidone is hepatically metabolized by cytochrome enzymes which mediates O-dealkylation (CYP3A4), hydroxylation (CYP2D6), and decarboxylation/reduction processes. Metabolites formed are P89, P95, and P88. The minor metabolite is P89, whereas P95 and P88 are the major ones. The affinity of the iloperidone metabolite P88 is generally equal or less than that of the parent compound. In contrast, the metabolite P95 only shows affinity for 5-HT2A (Ki value of 3.91) and the NEα1A, NEα1B, NEα1D, and NEα2C receptors (Ki values of 4.7, 2.7, 8.8 and 4.7 nM respectively).
▧ Route of Elimination :
Renal (in which <1% of iloperidone is excreted unchanged).
▧ Half Life :
The observed mean elimination half-lives for iloperidone, P88 and P95 in CYP2D6 extensive metabolizers (EM) are 18, 26 and 23 hours, respectively, and in poor metabolizers (PM) are 33, 37 and 31 hours, respectively.
▧ Clearance :
Apparent clearance (clearance/bioavilability) = 47-102 L/h.
Độc Tính : Commonly observed adverse reactions (incidence ≥5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.
Chỉ Định : Treatment of acute schizophrenia.
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Clarithromycin Clarithromycin is a strong CYP3A4 inhibitor that increases serum concentration of iloperidone. Reduce dose of iloperidone by 50%
  • Cocaine CYP2D6 Inhibitors (Strong) such as cocaine may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor.
  • Conivaptan CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor.
  • Fluoxetine Fluoxetine is a strong CYP2D6 inhibitor that increases serum concentration of iloperidone. Reduce dose of iloperidone by 50%
  • Ketoconazole Ketoconazole is a strong CYP3A4 inhibitor that increases serum concentration of iloperidone and likelihood of observing adverse effects such as QT prolongation. Reduce dose of iloperidone by 50%
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Paroxetine Paroxetine is a strong CYP2D6 inhibitor that increases serum concentration of iloperidone and likelihood of observing adverse effects such as QT prolongation. Reduce dose of iloperidone by 50%
  • Ziprasidone Additive QTc-prolongation may occur increasing the risk of life-threatening ventricular arrhythmias and torsade de pointes. Concomitant therapy should be avoided.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Tablet - Oral - 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Sản phẩm biệt dược : Fanapt
  • Công ty :
    Sản phẩm biệt dược : Fiapta
  • Công ty :
    Sản phẩm biệt dược : Zomaril
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04946
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=71360
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=12014542
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02666
ChemSpider
http://www.chemspider.com/Chemical-Structure.64459.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50034043
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/43068-110-02
PharmGKB
http://www.pharmgkb.org/drug/PA161199368
Wikipedia
http://en.wikipedia.org/wiki/Iloperidone
RxList
http://www.rxlist.com/fanapt-drug.htm
Drugs.com
http://www.drugs.com/fanapt.html
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