Tigecycline
|
| Systematic (IUPAC) name |
| N-[(5aR,6aS,7S,9Z,10aS)-9-[amino(hydroxy)methylidene]-4,7-bis(dimethylamino)-1,10a,12-trihydroxy-8,10,11-trioxo-5,5a,6,6a,7,8,9,10,10a,11-decahydrotetracen-2-yl]-2-(tert-butylamino)acetamide |
| Clinical data |
| Trade names |
Tygacil |
| AHFS/Drugs.com |
monograph |
|
Pregnancy
category
|
- AU: D
- US: D (Evidence of risk)
|
|
Legal status
|
- AU: Prescription Only (S4)
- US: ℞-only
|
|
Routes of
administration
|
IV only |
| Pharmacokinetic data |
| Bioavailability |
NA |
| Protein binding |
71-89% |
| Metabolism |
not metabolised |
| Half-life |
42.4 hours |
| Excretion |
59% biliary, 33% renal |
| Identifiers |
|
CAS Registry Number
|
220620-09-7 Y |
|
ATC code
|
J01AA12 |
| PubChem |
CID 5282044 |
| DrugBank |
DB00560 Y |
| ChemSpider |
10482314 Y |
| UNII |
70JE2N95KR Y |
| KEGG |
D01079 Y |
| ChEBI |
CHEBI:149836 Y |
| ChEMBL |
CHEMBL376140 Y |
| Synonyms |
N-[(5aR,6aS,7S,9Z,10aS)-9-(amino-hydroxy-methylidene)-4,7-bis(dimethylamino)-1,10a,12-trihydroxy-8,10,11-trioxo-5a,6,6a,7-tetrahydro-5H-tetracen-2-yl]-2-(tert-butylamino)acetamide |
| Chemical data |
| Formula |
C29H39N5O8 |
|
Molecular mass
|
585.65 g/mol |
SMILES
- CC(C)(C)NCC(=O)Nc1cc(c2C[C@H]3C[C@H]4[C@H](N(C)C)C(\O)=C(\C(N)=O)C(=O)[C@@]4(O)C(/O)=C3/C(=O)c2c1O)N(C)C
|
InChI
-
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 Y
Key:FPZLLRFZJZRHSY-HJYUBDRYSA-N Y
|
| Y (what is this?) (verify) |
Tigecycline (INN) // is a glycylcycline antibiotic[1][2] marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration (FDA) fast-track approval and was approved on June 17, 2005. It was developed in response to the growing prevalence of antibiotic resistance in bacteria such as Staphylococcus aureus and Acinetobacter baumannii. The New Delhi metallo-β-Lactamase multidrug-resistant Enterobacteriaceae has also shown susceptibility to tigecycline.[3]
Contents
- 1 Structure
- 2 Mechanism of action
- 3 Indications
- 4 Susceptibility data
- 5 Dosing
- 6 Side effects
- 7 Other uses
- 8 Synonyms
- 9 References
- 10 External links
Structure
This antibiotic is the first clinically available drug in a new class of antibiotics called the glycylcyclines. It is structurally similar to the tetracyclines in that it contains a central four-ring carbocyclic skeleton and is actually a derivative of minocycline. Tigecycline has a substitution at the D-9 position which is believed to confer broad spectrum activity.
Mechanism of action
Tigecycline is bacteriostatic and is a protein synthesis inhibitor by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of Aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation.[4]
Indications
Tigecycline is given intravenously and has activity against a variety of Gram-positive and Gram-negative bacterial pathogens, many of which are resistant to existing antibiotics. Tigecycline successfully completed phase III trials in which it was at least equal to intravenous vancomycin and aztreonam to treat complicated skin and skin structure infections (cSSSI), and to intravenous imipenem and cilastatin to treat complicated intra-abdominal infections (cIAI).[5] Tigecycline is active against many Gram-positive bacteria, Gram-negative bacteria and anaerobes – including activity against methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Haemophilus influenzae, and Neisseria gonorrhoeae (with MIC values reported at 2 µg/mL) and multi-drug resistant strains of Acinetobacter baumannii. It has no activity against Pseudomonas spp. or Proteus spp. The drug is licenced for the treatment of skin and soft tissue infections as well as intra-abdominal infections.
Susceptibility data
Tigecycline targets both Gram positive and Gram negative bacteria including a few key multi-drug resistant pathogens. The following represents MIC susceptibility data for a few medically significant bacterial pathogens.
- Escherichia coli: 0.015 μg/ml - 4 μg/ml
- Klebsiella pneumoniae: 0.06 μg/ml - 16 μg/ml
- Staphylococcus aureus (methicillin-resistant): 0.03 μg/ml - 2 μg/ml
[6]
Dosing
Tigecycline is given by slow intravenous infusion (30 to 60 minutes). A single dose of 100 mg is given first, followed by 50 mg every twelve hours after that. Patients with impaired liver function need to be given a lower dose. No adjustment is needed for patients with impaired kidney function. It is not licensed for use in children. There is no oral form available.
Side effects
Tigecycline has similar side effects to the tetracyclines. The most common side effects of tigecycline are diarrhea, nausea and vomiting. Nausea and vomiting is mild or moderate and usually occurs during the first two days of therapy. Other side effects include pain at the injection site, swelling and irritation; increased or decreased heart rate and infections. Also avoid use in children and pregnancy, due to its effects on teeth and bone. As with other antibiotics, overgrowth of organisms that are not susceptible to tigecycline can occur.
Tigecycline showed an increased mortality in patients treated for hospital-acquired pneumonia, especially ventilator-associated pneumonia (a non-approved use), but also in patients with complicated skin and skin structure infections, complicated intra-abdominal infections and diabetic foot infection. Increased mortality was in comparison to other treatment of the same types of infections. The difference was not statistically significant for any type, but mortality was numerically greater for every infection type with Tigecycline treatment, and prompted a black box warning by the FDA. [7]
Other uses
It may have potential for use in acute myeloid leukemia.[8]
Synonyms
References
- ^ Rose W, Rybak M (2006). "Tigecycline: first of a new class of antimicrobial agents.". Pharmacotherapy 26 (8): 1099–110. doi:10.1592/phco.26.8.1099. PMID 16863487.
- ^ Kasbekar N (2006). "Tigecycline: a new glycylcycline antimicrobial agent.". Am J Health Syst Pharm 63 (13): 1235–43. doi:10.2146/ajhp050487. PMID 16790575.
- ^ Kumarasamy et al. (2010). "Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study". The Lancet Infectious Diseases 10 (9): 597–602. doi:10.1016/S1473-3099(10)70143-2. PMC 2933358. PMID 20705517.
- ^ Tigecycline: A Novel Broad-Spectrum Antimicrobial: Pharmacology and Mechanism of Action Christine M. Slover, PharmD, Infectious Diseases Fellow, Keith A. Rodvold, PharmD and Larry H. Danziger, PharmD, Professor, Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL
- ^ Scheinfeld, N (2005). "Tigecycline: a review of a new glycylcycline antibiotic.". Journal of Dermatological Treatment 16 (4): 207–12. doi:10.1080/09546630510011810. PMID 16249141.
- ^ http://www.toku-e.com/Assets/MIC/Tigecycline.pdf
- ^ http://www.fda.gov/Drugs/DrugSafety/ucm224370.htm
- ^ Skrtić M, Sriskanthadevan S, Jhas B, Gebbia M, Wang X, Wang Z, Hurren R, Jitkova Y, Gronda M, Maclean N, Lai CK, Eberhard Y, Bartoszko J, Spagnuolo P, Rutledge AC, Datti A, Ketela T, Moffat J, Robinson BH, Cameron JH, Wrana J, Eaves CJ, Minden MD, Wang JC, Dick JE, Humphries K, Nislow C, Giaever G, Schimmer AD (2011) Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. Cancer Cell 20(5):674-688
- ^ Betriu C, Rodríguez-Avial I, Sánchez BA, Gómez M, Picazo JJ (2002). "Comparative in vitro activities of tigecycline (GAR-936) and other antimicrobial agents against Stenotrophomonas maltophilia". J Antimicrob Chemother 50 (5): 758–59. doi:10.1093/jac/dkf196. PMID 12407139.
External links
- Tygacil ( tigecycline iv ): Antibiotic for Skin Infections
|
Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ)
|
|
| 30S |
Aminoglycosides
(initiation inhibitors) |
| -mycin (Streptomyces) |
- Streptomycin#
- Dihydrostreptomycin
- Neomycin#
- Framycetin
- Paromomycin
- Ribostamycin
- Kanamycin#
- Amikacin
- Arbekacin
- Bekanamycin
- Dibekacin
- Tobramycin
- Spectinomycin#
- Hygromycin B
|
|
| -micin (Micromonospora) |
- Gentamicin#
- Netilmicin
- Sisomicin
- Isepamicin
|
|
|
Tetracycline antibiotics
(tRNA binding) |
| Tetracyclines |
- Doxycycline#
- Chlortetracycline
- Clomocycline
- Demeclocycline
- Lymecycline
- Meclocycline
- Metacycline
- Minocycline
- Oxytetracycline
- Penimepicycline
- Rolitetracycline
- Tetracycline
|
|
| Glycylcyclines |
|
|
|
|
| 50S |
Oxazolidinone
(initiation inhibitors) |
- Eperezolid
- Linezolid
- Posizolid
- Radezolid
- Ranbezolid
- Sutezolid
- Tedizolid
|
|
| Peptidyl transferase |
| Amphenicols |
- Chloramphenicol#
- Azidamfenicol
- Thiamphenicol
- Florfenicol
|
|
| Pleuromutilins |
- Retapamulin
- Tiamulin
- Valnemulin
|
|
|
| MLS (transpeptidation/translocation) |
| Macrolides |
- Azithromycin#
- Clarithromycin
- Dirithromycin
- Erythromycin#
- Flurithromycin
- Josamycin
- Midecamycin
- Miocamycin
- Oleandomycin
- Rokitamycin
- Roxithromycin
- Spiramycin
- Troleandomycin
- Tylosin
- Ketolides
- Telithromycin
- Cethromycin
- Solithromycin†
|
|
| Lincosamides |
- Clindamycin#
- Lincomycin
- Pirlimycin
|
|
| Streptogramins |
- Pristinamycin
- Quinupristin/dalfopristin
- Virginiamycin
|
|
|
|
| EF-G |
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
Index of bacterial disease
|
|
| Description |
|
|
| Disease |
- Gram-positive firmicutes
- Gram-positive actinobacteria
- Gram-negative proteobacteria
- Gram-negative non-proteobacteria
- Cholera
- Tuberculosis
|
|
| Treatment |
- Antibiotics
- cell wall
- nucleic acid
- mycobacteria
- protein synthesis
- other
- Antibodies
- Vaccines
|
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