Saxagliptin
Các tên gọi khác (4
) :
- (1S,3S,5S)-2-((2S)-Amino(3-hydroxytricyclo(3.3.1.13,7)dec-1-yl)acetyl)-2-azabicyclo(3.1.0)hexane-3-carbonitrile
- BMS 477118
- BMS-477118
- Onglyza
dipeptidyl peptidase iv inhibitors, antidiabetic agents
Thuốc Gốc
Small Molecule
CAS: 361442-04-8
ATC: A10BH03
CTHH: C18H25N3O2
PTK: 315.41
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
Phân tử khối
315.41
Monoisotopic mass
315.194677059
InChI
InChI=1S/C18H25N3O2/c19-8-13-2-12-3-14(12)21(13)16(22)15(20)17-4-10-1-11(5-17)7-18(23,6-10)9-17/h10-15,23H,1-7,9,20H2/t10?,11?,12-,13+,14+,15-,17?,18?/m1/s1
InChI Key
InChIKey=QGJUIPDUBHWZPV-SGTAVMJGSA-N
IUPAC Name
(1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile
Traditional IUPAC Name
saxagliptin
SMILES
N[C@H](C(=O)N1[C@H]2C[C@H]2C[C@H]1C#N)C12CC3CC(CC(O)(C3)C1)C2
Độ hòa tan
Sparingly soluble
logP
-0.08
logS
-2.1
pKa (strongest acidic)
14.74
pKa (Strongest Basic)
7.9
PSA
90.35 Å2
Refractivity
83.99 m3·mol-1
Polarizability
34.22 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
4
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học :
Cơ Chế Tác Dụng :
Dược Động Học :
Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. Saxagliptin did not accumulate following repeated doses. The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Bioavailability, 2.5 - 50 mg dose = 67%
▧ Volume of Distribution :
151 L
▧ Protein binding :
The in vitro protein binding of saxagliptin and its active metabolite in human serum is negligible (<10%).
▧ Metabolism :
The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). 50% of the absorbed dose will undergo hepatic metabolism. The major metabolite of saxagliptin, 5-hydroxy saxagliptin, is also a DPP4 inhibitor, which is one-half as potent as saxagliptin.
▧ Route of Elimination :
Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract.
▧ Half Life :
Saxagliptin = 2.5 hours; 5-hydroxy saxagliptin = 3.1 hours;
▧ Clearance :
Renal clearance, single 50 mg dose = 14 L/h
Độc Tính :
Chỉ Định :
Tương Tác Thuốc :
- Clarithromycin Clarithromycin is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
- Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Limit saxagliptin dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) with concomitant administration of a strong CYP3A4 inhibitor (e.g., ketoconazole). Monitor for decreased saxagliptin levels/effects with discontinuation of concomitant CYP3A4 inhibitor.
- Diltiazem Diltiazem is a moderate inhibitor of CYP3A4 and increases AUC of saxagliptin by 109%. Exposure of the active metabolite decreased by 34%. However, these changes in pharmacokinetics are not clinical significant.
- Erythromycin Erythromycin is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
- Indinavir Indinavir is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
- Ketoconazole Ketoconazole is a strong inhibitor of CYP3A4/5 which increases exposure of saxagliptin. The exposure of the active metabolite, 5-hydroxy saxagliptin, also decreases. Decrease dose of saxagliptin to 2.5 mg per day.
- Nefazodone Nefazodone is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
- Nelfinavir Nelfinavir is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
- Rifampicin Rifampin is a strong inducer of CYP3A4 which decreases exposure of saxagliptin. The exposure of the active metabolite, 5-hydroxy saxagliptin, also increases.
- Ritonavir Ritonavir is an inhibitor of CYP3A4 which increases exposure of saxagliptin. Decrease dose of saxagliptin to 2.5 mg per day.
- Simvastatin Simvastatin is a moderate inhibitor of CYP3A4 and increases AUC of saxagliptin by 12%. Exposure of the active metabolite decreased by 2%. However, these changes in pharmacokinetics are not clinical significant.
- Somatropin recombinant Somatropin may antagonize the hypoglycemic effect of saxagliptin. Monitor for changes in fasting and postprandial blood sugars.
- Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of saxagliptin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of saxagliptin if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng :
Tablet - Oral - 2.5 mg, 5 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
-
Công ty : Bristol-Myers SquibbSản phẩm biệt dược : Onglyza
Tài Liệu Tham Khảo Thêm
drugbank
PubChem Compound
PubChem Substance
National Drug Code Directory
Wikipedia
Bạn thấy hài lòng ?
Bạn chưa hài lòng ?
... loading
... loading