U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C29H39N5O8
Molecular Weight 585.6498
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIGECYCLINE

SMILES

CC(C)(C)NCC(=Nc1cc(c2C[C@@]3([H])C[C@@]4([H])[C@@]([H])(C(=C(C(=O)[C@]4(C(=C3C(=O)c2c1O)O)O)C(=N)O)O)N(C)C)N(C)C)O

InChI

InChIKey=FPZLLRFZJZRHSY-HJYUBDRYSA-N
InChI=1S/C29H39N5O8/c1-28(2,3)31-11-17(35)32-15-10-16(33(4)5)13-8-12-9-14-21(34(6)7)24(38)20(27(30)41)26(40)29(14,42)25(39)18(12)23(37)19(13)22(15)36/h10,12,14,21,31,36,38-39,42H,8-9,11H2,1-7H3,(H2,30,41)(H,32,35)/t12-,14-,21-,29-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00560 https://en.wikipedia.org/wiki/Tigecycline

Tigecycline (INN) is an antibiotic used to treat a number of bacterial infections. It is a first in class glycylcycline that is administered intravenously. For the treatment of infections caused by susceptible strains of the designated microorganisms in the following conditions: Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes and Bacteroides fragilis. Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros. Tigecycline, a glycylcycline, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. In general, tigecycline is considered bacteriostatic; however, TYGACIL has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila. In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterials.

CNS Activity

Curator's Comment:: On average, the systemic exposure of tigecycline in bone, SF and CSF ranged from 11% to 41% of serum concentrations.

Originator

Curator's Comment:: # Wyeth Pharmaceuticals

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
TYGACIL

Approved Use

is a tetracycline-class antibacterial drug indicated in patients 18 years of age and older for: Complicated skin and skin structure infections; Complicated intra-abdominal infections; Community-acquired bacterial pneumonia; Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia

Launch Date

1.14177606E12
Curative
TYGACIL

Approved Use

is a tetracycline-class antibacterial drug indicated in patients 18 years of age and older for: Complicated skin and skin structure infections; Complicated intra-abdominal infections; Community-acquired bacterial pneumonia; Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia

Launch Date

1.14177606E12
Curative
TYGACIL

Approved Use

is a tetracycline-class antibacterial drug indicated in patients 18 years of age and older for: Complicated skin and skin structure infections; Complicated intra-abdominal infections; Community-acquired bacterial pneumonia; Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia

Launch Date

1.14177606E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.63 μg/mL
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4.7 μg × h/mL
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
7.64 mg*h/L
100 mg single, intravenous
dose: 100 mg
route of administration: intravenous
experiment type: single
co-administered:
TIGECYCLINE serum
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
42.4 h
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
11%
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day multiple, intravenous
Highest studied dose
Dose: 100 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Disc. AE: Gastrointestinal disorder (NOS)...
AEs leading to
discontinuation/dose reduction:
Gastrointestinal disorder (NOS) (50%)
Sources: Page: p.223
300 mg single, intravenous
Highest studied dose
Dose: 300 mg
Route: intravenous
Route: single
Dose: 300 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
DLT: Gastrointestinal disorder NOS...
Dose limiting toxicities:
Gastrointestinal disorder NOS
Sources: Page: p.223
100 mg single, intravenous
MTD
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (50%)
Vomiting (50%)
Sources: Page: p.223
200 mg single, intravenous
MTD
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea
Vomiting
Sources: Page: p.223
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.10
unhealthy
n = 3788
Health Status: unhealthy
Condition: Complicated skin and skin structure infections
Population Size: 3788
Sources: Page: p.10
Disc. AE: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Nausea (1%)
Vomiting (1%)
Sources: Page: p.10
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Disc. AE: Anaphylaxis, Anaphylactoid reaction...
AEs leading to
discontinuation/dose reduction:
Anaphylaxis
Anaphylactoid reaction
Hepatic dysfunction NOS
Liver failure
Pancreatitis (grade 5)
Fetal damage
Tooth discoloration
Diarrhea, Clostridium difficile
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorder (NOS) 50%
Disc. AE
100 mg 2 times / day multiple, intravenous
Highest studied dose
Dose: 100 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 100 mg, 2 times / day
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Gastrointestinal disorder NOS DLT
300 mg single, intravenous
Highest studied dose
Dose: 300 mg
Route: intravenous
Route: single
Dose: 300 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Nausea 50%
100 mg single, intravenous
MTD
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Vomiting 50%
100 mg single, intravenous
MTD
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Nausea
200 mg single, intravenous
MTD
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Vomiting
200 mg single, intravenous
MTD
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources: Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources: Page: p.223
Nausea 1%
Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.10
unhealthy
n = 3788
Health Status: unhealthy
Condition: Complicated skin and skin structure infections
Population Size: 3788
Sources: Page: p.10
Vomiting 1%
Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.10
unhealthy
n = 3788
Health Status: unhealthy
Condition: Complicated skin and skin structure infections
Population Size: 3788
Sources: Page: p.10
Anaphylactoid reaction Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Anaphylaxis Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Diarrhea, Clostridium difficile Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Fetal damage Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Hepatic dysfunction NOS Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Liver failure Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Tooth discoloration Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Pancreatitis grade 5
Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources: Page: p.1
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
inconclusive
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Disk diffusion susceptibility test development for the new glycylcycline, GAR-936.
1999 Nov
Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1,203 recent clinical bacterial isolates.
2000 Jan
Comparison of the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria.
2002 Oct
Tigecycline: first of a new class of antimicrobial agents.
2006 Aug
Tigecycline: a new glycylcycline antimicrobial agent.
2006 Jul 1
Meticillin-resistant Staphylococcus aureus hepatic abscess treated with tigecycline.
2008 Aug
Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001-06.
2008 Nov
Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of the Canadian Ward Surveillance Study (CANWARD 2008).
2010 Nov
Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent.
2012 Jan 26
Tigecycline prevents LPS-induced release of pro-inflammatory and apoptotic mediators in neuronal cells.
2013 Mar
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

Initial dose of 100 mg, followed by 50 mg every 12 hours administered intravenously over approximately 30 to 60 minutes. Severe hepatic impairment (Child Pugh C): Initial dose of 100 mg followed by 25 mg every 12 hours.
Route of Administration: Intravenous
In Vitro Use Guide
Among the tested gram-positive isolates, tigecycline was most active as reflected by MIC50/MIC90 values against S. pyogenes (0.03/0.03 μg/ml) and S. pneumoniae (0.015/0.03 μg/ml), followed by S. aureus (0.12/0.25 μg/ml) and E. faecalis (0.12/0.5 μg/ml)
Name Type Language
TIGECYCLINE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
TIGECYCLINE [USAN]
Common Name English
TIGECYCLINE [USP-RS]
Common Name English
TIGECYCLINE [USP MONOGRAPH]
Common Name English
TIGECYCLINE [INN]
Common Name English
TIGECYCLINE [VANDF]
Common Name English
TIGECYCLINE [EP MONOGRAPH]
Common Name English
(4S,4AS,5AR,12AS)-9-(2-(TERT-BUTYLAMINO)ACETAMIDO)-4,7-BIS(DIMETHYLAMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-2-NAPHTHACENECARBOXAMIDE
Common Name English
TIGECYCLINE [WHO-DD]
Common Name English
2-NAPHTHACENECARBOXAMIDE, 4,7-BIS(DIMETHYLAMINO)-9-((((1,1-DIMETHYLETHYL)AMINO)ACETYL)AMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-, (4S,4AS,5AR,12AS)-
Common Name English
WAY-GAR-936
Code English
TIGECYCLINE [MI]
Common Name English
TYGACIL
Brand Name English
TIGECYCLINE [ORANGE BOOK]
Common Name English
TIGECYCLINE [JAN]
Common Name English
TIGECYCLINE [MART.]
Common Name English
TIGECYCLINE [EMA EPAR]
Common Name English
Classification Tree Code System Code
WHO-ATC J01AA12
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
NDF-RT N0000007948
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
NDF-RT N0000175938
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
WHO-VATC QJ01AA12
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
FDA ORPHAN DRUG 406313
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
NDF-RT N0000007948
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
EMA ASSESSMENT REPORTS TYGACIL (AUTHORIZED SOFT TISSUE INFECTIONS)
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
LIVERTOX 964
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
NCI_THESAURUS C258
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
Code System Code Type Description
CAS
220620-09-7
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
MESH
C119092
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
EPA CompTox
220620-09-7
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
LACTMED
Tigecycline
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
INN
8115
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
ChEMBL
CHEMBL376140
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
MERCK INDEX
M10858
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C72865
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
USP_CATALOG
1667643
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY USP-RS
FDA UNII
70JE2N95KR
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
DRUG BANK
DB00560
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
EVMPD
SUB16467MIG
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
RXCUI
384455
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
TIGECYCLINE
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
DRUG CENTRAL
2661
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY
HSDB
8172
Created by admin on Fri Jun 25 21:08:11 UTC 2021 , Edited by admin on Fri Jun 25 21:08:11 UTC 2021
PRIMARY