Tìm theo
Alogliptin
Các tên gọi khác (4 ) :
  • Alogliptina
  • Alogliptine
  • Alogliptinum
  • SYR-322
Insulin và nhóm Thuốc hạ đường huyết
Thuốc Gốc
Small Molecule
CAS: 850649-61-5
ATC: A10BH04
CTHH: C18H21N5O2
PTK: 339.3916
Alogliptin is a selective, orally-bioavailable inhibitor of enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt and exists predominantly as the R-enantiomer (>99%). It undergoes little or no chiral conversion in vivo to the (S)-enantiomer. FDA approved January 25, 2013.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H21N5O2
Phân tử khối
339.3916
Monoisotopic mass
339.169524941
InChI
InChI=1S/C18H21N5O2/c1-21-17(24)9-16(22-8-4-7-15(20)12-22)23(18(21)25)11-14-6-3-2-5-13(14)10-19/h2-3,5-6,9,15H,4,7-8,11-12,20H2,1H3/t15-/m1/s1
InChI Key
InChIKey=ZSBOMTDTBDDKMP-OAHLLOKOSA-N
IUPAC Name
2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl}methyl)benzonitrile
Traditional IUPAC Name
alogliptin
SMILES
CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Độ hòa tan
Sparingly soluble
logP
1.16
logS
-2.8
pKa (Strongest Basic)
9.47
PSA
93.67 Å2
Refractivity
104.26 m3·mol-1
Polarizability
35.44 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
5
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.
Cơ Chế Tác Dụng : Alogliptin is a selective, orally-bioavailable inhibitor of enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt and exists predominantly as the R-enantiomer (>99%). It undergoes little or no chiral conversion in vivo to the (S)-enantiomer. FDA approved January 25, 2013. Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.
Dược Động Học :
▧ Absorption :
The pharmacokinetics of NESINA was also shown to be similar in healthy subjects and in patients with type 2 diabetes. When single, oral doses up to 800 mg in healthy subjects and type 2 diabetes patients are given, the peak plasma alogliptin concentration (median Tmax) occurred 1 to 2 hours after dosing. Accumulation of aloglipin is minimal. The absolute bioavailability of NESINA is approximately 100%. Food does not affect the absorption of alogliptin.
▧ Volume of Distribution :
Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is well distributed into tissues.
▧ Protein binding :
Alogliptin is 20% bound to plasma proteins.
▧ Metabolism :
Alogliptin does not undergo extensive metabolism. Two minor metabolites that were detected are N-demethylated alogliptin (<1% of parent compound) and N-acetylated alogliptin (<6% of parent compound). The N-demethylated metabolite is active and an inhibitor of DPP-4. The N-acetylated metabolite is inactive. Cytochrome enzymes that are involved with the metabolism of alogliptin are CYP2D6 and CYP3A4 but the extent to which this occurs is minimal. Approximately 10-20% of the dose is hepatically metabolized by cytochrome enzymes.
▧ Route of Elimination :
Renal excretion (76%) and feces (13%). 60% to 71% of the dose is excreted as unchanged drug in the urine.
▧ Half Life :
Terminal half-life = 21 hours
▧ Clearance :
Renal clearance = 9.6 L/h (this value indicates some active renal tubular secretion); Systemic clearance = 14.0 L/h.
Độc Tính : Common adverse reactions (reported in ≥4% of patients treated with alogliptin 25 mg and more frequently than in patients who received placebo) are: nasopharyngitis, headache, and upper respiratory tract infection.
Chỉ Định : Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Liều Lượng & Cách Dùng : Tablet - Oral - 6.25 mg, 12.5 mg, 25 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06203
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06553
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/64764-250-30
Wikipedia
http://en.wikipedia.org/wiki/Alogliptin
RxList
http://www.rxlist.com/nesina-drug/patient-images-side-effects.htm
Drugs.com
http://www.drugs.com/mtm/alogliptin.html
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