Tìm theo
Linagliptin
Các tên gọi khác (5 ) :
  • (R)-8-(3-Aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methylquinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione
  • BI 1356
  • BI-1356
  • Tradjenta
  • Trajenta
dipeptidyl peptidase iv inhibitors, antidiabetic agents
Thuốc Gốc
Small Molecule
CAS: 668270-12-0
ATC: A10BH05
CTHH: C25H28N8O2
PTK: 472.5422
Linagliptin is a DPP-4 inhibitor developed by Boehringer Ingelheim for the treatment of type II diabetes [Wikipedia]. Two pharmacological characteristics that sets linagliptin apart from other DPP-4 inhibitors is that it has a non-linear pharmacokinetic profile and is not primarily eliminated by the renal system. FDA approved on May 2, 2011.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C25H28N8O2
Phân tử khối
472.5422
Monoisotopic mass
472.23352218
InChI
InChI=1S/C25H28N8O2/c1-4-5-13-32-21-22(29-24(32)31-12-8-9-17(26)14-31)30(3)25(35)33(23(21)34)15-20-27-16(2)18-10-6-7-11-19(18)28-20/h6-7,10-11,17H,8-9,12-15,26H2,1-3H3/t17-/m1/s1
InChI Key
InChIKey=LTXREWYXXSTFRX-QGZVFWFLSA-N
IUPAC Name
8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione
Traditional IUPAC Name
linagliptin
SMILES
CC#CCN1C(=NC2=C1C(=O)N(CC1=NC3=C(C=CC=C3)C(C)=N1)C(=O)N2C)N1CCC[C@@H](N)C1
Độ hòa tan
<1 mg/mL
logP
2.8
logS
-4
pKa (Strongest Basic)
9.86
PSA
113.48 Å2
Refractivity
133.43 m3·mol-1
Polarizability
51.97 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
7
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
Dược Lực Học : Linagliptin is a more potent inhibitor of DPP-4 than other drugs that belong to the same class with an IC50 of 1 nM. In comparison, sitagliptin, saxagliptin, and vildagliptin have an IC50 of 19, 50, and 62 nM respectively. A dose of 2.5 and 5 mg reduces the activity of DPP-4 by 72.7% and 86.1% from baseline respectively in healthy male subjects. In diabetes patients, a dose of 5 and 10 mg inhibits >90% of DPP-4. Linagliptin is also selectively inhibits DPP-4 as indicated by the lack of DPP-8 or DPP-9 inhibition at therapeutic exposures in vitro.
Cơ Chế Tác Dụng : Linagliptin is a DPP-4 inhibitor developed by Boehringer Ingelheim for the treatment of type II diabetes [Wikipedia]. Two pharmacological characteristics that sets linagliptin apart from other DPP-4 inhibitors is that it has a non-linear pharmacokinetic profile and is not primarily eliminated by the renal system. FDA approved on May 2, 2011. Linagliptin is a competitive and reversible dipeptidyl peptidase (DPP)-4 enzyme inhibitor that slows the breakdown of insulinotropic hormone glucagon-like peptide (GLP)-1 for better glycemic control in diabetes patients. GLP and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that increase the production and release of insulin from pancreatic beta cells and decrease the release of glucagon from pancreatic alpha cells. This results in a overall decrease in glucose production in the liver and increase an of insulin in a glucose-dependent manner.
Dược Động Học :
▧ Absorption :
Cmax, 5 mg, healthy subjects = 8.32 nmol/L; Tmax, 5 mg, healthy subjects = 1.75 hours; AUC(0-24 hours), 5 mg, healthy subjects = 119 nmol · h/L; Bioavailability, healthy subjects = 30%. When a dose of 5 mg once daily is given, steady state is achieved by the third dose. Although a high fat meal reduces Cmax and increases AUC, this interaction with food is not clinically significant. Linagliptin may be administered with or without food.
▧ Volume of Distribution :
Vd = 1110 L
▧ Protein binding :
70-80% protein bound, the extent to which is concentration dependent. Because of the propensity of linagliptin to bind to plasma protein, it has a long terminal half-life and a non-linear pharmacokinetic profile. In contrast, other DPP-4 inhibitors have linear pharmacokinetic profiles which makes linagliptin unique.
▧ Metabolism :
Linagliptin is not extensively metabolized, 90% of dose is excreted unchanged. The small portion of drug that is metabolized, the main metabolite is CD 1790 and is pharmacologically inactive. Glucuronidation forms some of its other minor metabolites.
▧ Route of Elimination :
Linagliptin is eliminated via the feces/enteroheptic system (80%) and urine (5%). This is unlike other DPP-4 inhibitors which are primarily eliminated by the renal system.
▧ Half Life :
Terminal half life = 131 hours. Because of this long half-life, inhibition of DPP-4 activity is sustained which indicates that once-daily dosing is appropriate. Effective half-life for accumulation of drug is 12 hours when multiple oral doses of 5 mg are given.
▧ Clearance :
Renal clearance, steady state = 70 mL/min
Chỉ Định : Linagliptin is used for the management of type 2 diabetes mellitus.
Tương Tác Thuốc :
  • Carbamazepine CYP3A4 and p-glycoprotein inducers may decreases levels of linagliptin. Monitor concomitant therapy closely.
  • Etravirine Linagliptin, when used concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy if possible, and to monitor linagliptin therapy if concurrent use cannot be avoided.
  • Hydrocortisone CYP3A4 inducers may decrease levels of linagliptin and diminish the hypoglycemic effect of antidiabetic agents. Monitor concomitant therapy closely.
  • Prednisone CYP3A4 inducers may decrease levels of linagliptin and diminish the hypoglycemic effect of antidiabetic agents. Monitor concomitant therapy closely.
  • Rifampicin CYP3A4 and p-glycoprotein inducers may decreases levels of linagliptin. Monitor concomitant therapy closely.
  • Ritonavir CYP3A4 inhibitors may increase levels of linagliptin. Monitor concomitant therapy closely.
Liều Lượng & Cách Dùng : Tablet - Oral - 5 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08882
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D09566
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0597-0146-60
Wikipedia
http://en.wikipedia.org/wiki/Linagliptin
RxList
http://www.rxlist.com/tradjenta-drug.htm
Drugs.com
http://www.drugs.com/cdi/linagliptin.html
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