Tìm theo
Lomitapide
Các tên gọi khác (2) :
  • AEGR 733
  • BMS 201038
hypolipidemic agents
Thuốc Gốc
Small Molecule
CAS: 182431-12-5
ATC: C10AX12
CTHH: C39H37F6N3O2
PTK: 693.7204
Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor used in homozygous familial hypercholesterolemia (HoFH) patients. It is marketed under the name Juxtapid (R).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C39H37F6N3O2
Phân tử khối
693.7204
Monoisotopic mass
693.278996673
InChI
InChI=1S/C39H37F6N3O2/c40-38(41,42)25-46-36(50)37(33-13-5-3-10-30(33)31-11-4-6-14-34(31)37)21-7-8-22-48-23-19-28(20-24-48)47-35(49)32-12-2-1-9-29(32)26-15-17-27(18-16-26)39(43,44)45/h1-6,9-18,28H,7-8,19-25H2,(H,46,50)(H,47,49)
InChI Key
InChIKey=MBBCVAKAJPKAKM-UHFFFAOYSA-N
IUPAC Name
N-(2,2,2-trifluoroethyl)-9-[4-(4-{2-[4-(trifluoromethyl)phenyl]benzamido}piperidin-1-yl)butyl]-9H-fluorene-9-carboxamide
Traditional IUPAC Name
lomitapide
SMILES
FC(F)(F)CNC(=O)C1(CCCCN2CCC(CC2)NC(=O)C2=C(C=CC=C2)C2=CC=C(C=C2)C(F)(F)F)C2=CC=CC=C2C2=CC=CC=C12
logP
7.7
pKa (strongest acidic)
10.35
pKa (Strongest Basic)
9.02
PSA
61.44 Å2
Refractivity
181.73 m3·mol-1
Polarizability
68.08 Å3
Rotatable Bond Count
12
H Bond Acceptor Count
3
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
6
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Lomitapide directly inhibits microsomal triglyceride transfer protein (MTP).
Cơ Chế Tác Dụng : Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor used in homozygous familial hypercholesterolemia (HoFH) patients. It is marketed under the name Juxtapid (R). Within the lumen of the endoplasmic reticulum, lomitapide inhibits microsomal triglyceride transfer protein (MTP), which prevents the formation of apolipoprotein B, and, thus, the formation of VLDL and chylomicrons as well. Altogether, this leads to a reduction of low-density lipoprotein cholesterol.
Dược Động Học :
▧ Absorption :
In healthy patients, time to maximum lomitapide concentration is about 6 hours with a single dose of 60 mg. Lomitapide has an approximate absolute bioavailability of 7%.
▧ Volume of Distribution :
The steady state volume of distribution is about 985-1292 L.
▧ Protein binding :
Plasma protein binding is about 99.8%
▧ Metabolism :
Lomitapide is mainly metabolized by CYP3A4 to it's inactive metabolites, M1 and M3. CYP enzymes that metabolize lomitapide to a minor extent include CYP 1A2,2B6,2C8,2C19.
▧ Route of Elimination :
About 52.9-59.5% is eliminated by the urine and 33.4-35.1% is eliminated by the feces.
▧ Half Life :
Lomitapide half-life is about 39.7 hours.
Độc Tính : Contra-indicated in pregnancy, and moderate to severe hepatic insufficiency (Child-Pugh category B or C). Severe GI adverse reactions may occur.
Chỉ Định : Used in homozygous familial hypercholesterolemia (HoFH) patients to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C).
Tương Tác Thuốc :
  • Atorvastatin Atorvastatin, and other weak CYP3A4 inhibitors (such as amiodarone, amlodipine, alprazolam, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginko, goldenseal, isoniazide, lapatinib, nilotinib, oral contraceptives, pazopanib, ranitidine, ranolazine, tipranavir/ritonavir, ticagrelor, zileuton) increase lomitapide levels by 2-fold. Thus lomipatide should be dosed at a maximum of 30mg daily when used concomitantly with weak inhibitors of CYP3A4.
  • Boceprevir Boceprevir increases levels of lomipatide by 27 folds by inhibiting CYP3A4 metabolism. Concomitant therapy of Boceprevir and strong CYP3A4 inhibitors (such as clarithromycin, conivaptan, indinavir, intraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, variconazole) with lomipatide is contraindicated.
  • Cholestyramine Bile acid sequestrants also used for treating high cholesterol may interfere with the absorption of oral medications, thus separate administration by 4 hours.
  • Ciprofloxacin The effect of coadminstration of lomipatide with ciproflaxacin, and other moderate CYP3A4 inhibitors (such as aprepitant, amprenavir, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) is unknown. However, as coadministration is likely to increase serum concentrations of lomipatide, concomitant use is contraindicated.
  • Colestipol Bile acid sequestrants also used for treating high cholesterol may interfere with the absorption of oral medications, thus separate administration by 4 hours.
  • Crizotinib Strong CYP3A4 inhibitors may increase levels of crizotinib. Concomitant therapy is contraindicated.
  • Dabigatran etexilate Dabigatran is a p-glycoprotien (P-gp) substrate. Levels of dabigatran may increase if coadministered with lomipatide, which is a P-gp inhibitor. Thus, it is recommended to dose reduce P-gp substrates (such as ambrisentan, aliskiren, colchicine, digoxin, everolimus, fexofenadine, imatinib, lapatinib, maraviroc, nilotinib, posaconazole, ranolazine, saxagliptin, sirolimus, sitagliptin, talinolol, tolvaptan, topotecan) with the concomitant use of lomipatide.
  • Lovastatin Lovastatin plasma concentrations may increase by lomitapide.
  • Simvastatin Simvastatin plasma concentrations are doubled by lomitapide. To prevent dose related adverse effects such as myopathy and rhabdomyolysis it is recommended to reduce the dose of simvastatin by 50%. See FDA label for additional dosage instructions.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • Ticagrelor Ticagrelor increases levels of lomitapide by affecting CYP3A4 enzyme metabolism. Concomitant therapy is contraindicated.
  • Warfarin Warfarin plasma concentrations may increase by lomitapide by 30%.. INR levels may increase by 22%. Regular INR monitoring is required.
Liều Lượng & Cách Dùng : Capsule - Oral - 10 mg
Capsule - Oral - 20 mg
Capsule - Oral - 5 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08827
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09637
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/76431-110-01
Wikipedia
http://en.wikipedia.org/wiki/Lomitapide
RxList
http://www.rxlist.com/juxtapid-drug.htm
Drugs.com
http://www.drugs.com/juxtapid.html
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