Vildagliptin

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H25N3O2
Molecular Weight	303.3993
Optical Activity	( - )
Defined Stereocenters	1 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

OC12CC3CC(C1)CC(C3)(C2)NCC(=O)N4CCC[C@H]4C#N

InChI

InChIKey=SYOKIDBDQMKNDQ-XWTIBIIYSA-N

InChI=1S/C17H25N3O2/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16/h12-14,19,22H,1-8,10-11H2/t12?,13?,14-,16?,17?/m0/s1

HIDE SMILES / InChI

Molecular Formula	C17H25N3O2
Molecular Weight	303.3993
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	MIXED
Additional Stereochemistry	No
Defined Stereocenters	1 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Vildagliptin, previously identified as LAF237, is a new oral anti-hyperglycemic agent (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucaon release by the alpha cells of the islets of Langerhans in the pancreas. It is currently in clinical trials in the U.S. and has been shown to reduce hyperglycemia in type 2 diabetes mellitus. While the drug is still not approved for use in the US, it was approved in Feb 2008 by European Medicines Agency for use within the EU and is listed on the Australian PBS with certain restrictions. Vildagliptin is marketed under the trade names Galvus, Zomelis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dipeptidyl peptidase IV 37	Inhibitor 8,297		62.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259	Primary		Approved 8,429	Galvus

C_max

Value	Dose	Analyte	Population
162 ng/mL	25 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
272 ng/mL	50 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
671 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
1959 ng/mL	200 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2860 ng/mL	400 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
524 ng/mL	50 mg 2 times / day multiple, oral	VILDAGLIPTIN plasma	Homo sapiens
415 ng/mL	50 mg 2 times / day multiple, oral	VILDAGLIPTIN plasma	Homo sapiens
538 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
431 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
675 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
497 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
512 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
632 ng/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
545 ng × h/mL	25 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
1139 ng × h/mL	50 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2968 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
6857 ng × h/mL	200 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
13420 ng × h/mL	400 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
1480 ng × h/mL	50 mg 2 times / day multiple, oral	VILDAGLIPTIN plasma	Homo sapiens
1490 ng × h/mL	50 mg 2 times / day multiple, oral	VILDAGLIPTIN plasma	Homo sapiens
2500 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2215 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2567 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2076 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2411 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
3322 ng × h/mL	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
1.54 h	25 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
1.77 h	50 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2.1 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2 h	200 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
5.29 h	400 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
1.78 h	50 mg 2 times / day multiple, oral	VILDAGLIPTIN plasma	Homo sapiens
2.41 h	50 mg 2 times / day multiple, oral	VILDAGLIPTIN plasma	Homo sapiens
2.1 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2.9 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
4.9 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
3.1 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens
2.4 h	100 mg single, oral	VILDAGLIPTIN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
90.7%			VILDAGLIPTIN plasma	Homo sapiens

Doses

Doses

Show entries

Dose	Population	Adverse events
400 mg 1 times / day multiple, oral Highest studied dose	healthy, ADULT
100 mg 1 times / day multiple, oral Recommended	unhealthy, ADULT

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PubMed

Show entries

Title	Date	PubMed
1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.	2003 Jun 19	12801240
Gateways to clinical trials.	2004 Nov	15632957
Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus.	2005	16318402
American Diabetes Association - 65th Scientific Sessions. DDP-IV inhibitors.	2005 Aug	16044362
Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.	2005 Aug	16043735

Showing 1 to 5 of 33 entries

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Patents

Sample Use Guides

In Vivo Use Guide

When used as monotherapy, in combination with metformin, in combination with thiazolidinedione, in combination with metformin and a sulphonylurea, or in combination with insulin (with or without metformin), the recommended daily dose of vildagliptin is 100 mg, administered as one dose of 50 mg in the morning and one dose of 50 mg in the evening. When used in dual combination with a sulphonylurea, the recommended dose of vildagliptin is 50 mg once daily administered in the morning. In this patient population, vildagliptin 100 mg daily was no more effective than vildagliptin 50 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Vildagliptin inhibited rat plasma DPP-IV activity in vitro with an IC(50) value of 2.12 nmol/l

Substance Class	Chemical
Record UNII	I6B4B2U96P
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

Vildagliptin

Official Name

English

VILDAGLIPTIN [USAN]

Common Name

English

LAF-237

Code

English

2-PYRROLIDINECARBONITRILE, 1-(((3-HYDROXYTRICYCLO(3.3.1.1(SUP 3,7))DEC-1-YL)AMINO)ACETYL)-, (2S)-

Systematic Name

English

EQUA

Brand Name

English

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Classification Tree

Code System

Code

Enzyme Inhibitor

NCI_THESAURUS

C98086

Combinations of oral blood glucose lowering drugs

WHO-ATC

A10BD08

Combinations of oral blood glucose lowering drugs

WHO-VATC

QA10BD08

Dipeptidyl peptidase 4 (DPP-4) inhibitors

WHO-VATC

QA10BH02

Dipeptidyl peptidase 4 (DPP-4) inhibitors

WHO-ATC

A10BH02

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Code System

Code

Type

Description

USAN

RR-71

PRIMARY

RXCUI

596554

PRIMARY

RxNorm

DRUG BANK

DB04876

PRIMARY

EPA CompTox

DTXSID80881091

PRIMARY

FDA UNII

I6B4B2U96P

PRIMARY

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Related Record

Type

Details


					I6B4B2U96P

Vildagliptin

EXCRETED UNCHANGED

Qualification:

FECAL

Amount:

4.54 % (average)
of the dose


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Comments:

The mean plasma protein binding of vildagliptin in humans was low (9.3%) and also independent of concentration.

Interaction Type:

BINDING

Amount:

9.3 % (average)


					9KND64V2AA

Vildagliptin hydrochloride

SALT/SOLVATE -> PARENT

Amount:


					I6B4B2U96P

Vildagliptin

EXCRETED UNCHANGED

Qualification:

URINE

Amount:

22.6 % (average)
of the dose


					RIGEZF4K05

DIPEPTIDYL PEPTIDASE 4 MEMBRANE FORM

TARGET -> INHIBITOR

Amount:

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Related Record

Type

Details


					3JZB9AHA39

2-((3-HYDROXYADAMANTAN-1-YL)AMINO)ACETIC ACID

METABOLITE -> PARENT

Qualification:

PLASMA

Amount:

8.1 % (average)
of the total plasma exposure


					TF6NS92SLH

L-PROLINE, N-(3-HYDROXYTRICYCLO(3.3.1.13,7)DEC-1-YL)GLYCYL-

METABOLITE -> PARENT

Qualification:

FECAL

Amount:

6.89 % (average)
of the administered dose


					TF6NS92SLH

L-PROLINE, N-(3-HYDROXYTRICYCLO(3.3.1.13,7)DEC-1-YL)GLYCYL-

METABOLITE -> PARENT

Interaction Type:

MAJOR

Qualification:

URINE

Amount:

49.6 % (average)
of the administered dose


					LF6DL44ERH

4-((2-((3-HYDROXYTRICYCLO(3.3.1.13,7)DEC-1-YL)AMINO)ACETYL)AMINO)BUTANOIC ACID

METABOLITE -> PARENT

Qualification:

URINE

Amount:

0.64 % (average)
of dose


					3JZB9AHA39

2-((3-HYDROXYADAMANTAN-1-YL)AMINO)ACETIC ACID

METABOLITE -> PARENT

Qualification:

FECAL

Amount:

0.26 % (average)
of the administered dose

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Related Record

Type

Details


					I6B4B2U96P

Vildagliptin

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount	Parameters
Tmax	PHARMACOKINETIC	1.1 hours [0.5 to 2] (average)	ORAL ADMINISTRATION

Biological Half-life	PHARMACOKINETIC	2.8 hours [1.8 to 3.8] (average)	ORAL ADMINISTRATION

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound