Cethromycin

Cethromycin, trade name Restanza (initially known as ABT-773^[1][2]) is a ketolide antibiotic undergoing research for the treatment of community acquired pneumonia (CAP)^[1][3][4][5] and for the prevention of post-exposure inhalational anthrax, and was given an "orphan drug" status for this indication.^[6] Originally discovered and developed by Abbott, it was acquired by Advanced Life Sciences Inc. for further development.

Cethromycin

Clinical data
Routes of administration	Oral
ATC code	none
Legal status
Legal status	US: Phase III Clinical Trials
Pharmacokinetic data
Bioavailability	Between 35.8 and 60% in animal studies.
Metabolism	Liver
Elimination half-life	1.6, 3.0, 4.5, 5.9 and 6 hours. Mouse, Monkey, Rat, Dog and Human respectively.
Excretion	7.0% urine 87.2% faeces
Identifiers
IUPAC name (1S,2R,5R,7R,8R,9S,11R,13R,14R)-8-[(2S,3R,4S,6R)- 4-Dimethylamino-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-1,5,7,9,11,13- hexamethyl-9-[(E)-3-quinolin-3-ylprop-2-enoxy] -3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone
CAS Number	205110-48-1 Y
PubChem CID	5282045
ChemSpider	23258189 N
UNII	J0086219X6
KEGG	D02391 N
ChEBI	CHEBI:29506
ChEMBL	ChEMBL365528 N
Chemical and physical data
Formula	C42H59N3O10
Molar mass	765.945 g·mol−1
3D model (JSmol)	Interactive image
Melting point	211 to 213 °C (412 to 415 °F)
SMILES CC[C@@H]1[C@@]2([C@@H]([C@H](C(=O)[C@@H](C[C@]([C@@H]([C@H](C(=O)[C@H](C(=O)O1)C)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC/C=C/c4cc5ccccc5nc4)C)C)NC(=O)O2)C
InChI InChI=1S/C42H59N3O10/c1-11-32-42(8)36(44-40(50)55-42)25(4)33(46)23(2)21-41(7,51-18-14-15-28-20-29-16-12-13-17-30(29)43-22-28)37(26(5)34(47)27(6)38(49)53-32)54-39-35(48)31(45(9)10)19-24(3)52-39/h12-17,20,22-27,31-32,35-37,39,48H,11,18-19,21H2,1-10H3,(H,44,50)/b15-14+/t23-,24-,25+,26+,27-,31+,32-,35-,36-,37-,39+,41+,42-/m1/s1 N Key:PENDGIOBPJLVBT-HMMOOPTJSA-N N
NY (what is this?)  (verify)

On October 1, 2008, Advanced Life Sciences submitted a New Drug Application (NDA) to Food and Drug Administration (FDA) for cethromycin to treat mild-to-moderate community acquired pneumonia.^[7]

On December 3, 2008, Advanced Life Sciences announced that this New Drug Application has been accepted for filing by the FDA.^[8]

In June 2009, an FDA Anti-Infective Drugs Advisory Committee review found insufficient evidence for cethromycin efficacy in treatment of community acquired pneumonia, as the Phase 3 clinical trial followed standards that were updated after the clinical trial but three months prior to review. The committee did, however, find the drug safe to use.^[9]

References

1. Lawrence LE (June 2001). "ABT-773 (Abbott Laboratories)". Current Opinion in Investigational Drugs. 2 (6): 766–72. PMID 11572654.
2. Dougherty TJ, Barrett JF (February 2001). "ABT-773: a new ketolide antibiotic". Expert Opinion on Investigational Drugs. 10 (2): 343–51. doi:10.1517/13543784.10.2.343. PMID 11178346. S2CID 21855657.
3. Zhanel GG, Hisanaga T, Nichol K, Wierzbowski A, Hoban DJ (November 2003). "Ketolides: an emerging treatment for macrolide-resistant respiratory infections, focusing on S. pneumoniae". Expert Opinion on Emerging Drugs. 8 (2): 297–321. doi:10.1517/14728214.8.2.297. PMID 14661991. S2CID 23004334.
4. Reinert RR (June 2004). "Clinical efficacy of ketolides in the treatment of respiratory tract infections". The Journal of Antimicrobial Chemotherapy. 53 (6): 918–27. doi:10.1093/jac/dkh169. PMID 15117934.
5. Hammerschlag MR, Sharma R (March 2008). "Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections". Expert Opinion on Investigational Drugs. 17 (3): 387–400. doi:10.1517/13543784.17.3.387. PMID 18321237. S2CID 70678060.
6. Cethromycin – Advanced Life Sciences Archived April 20, 2008, at the Wayback Machine
7. Cethromycin New Drug Application
8. Cethromycin New Drug Application accepted for filing by FDA^{[permanent dead link‍]}
9. Advanced Life Sciences Holdings, Inc. "Complete Response Letter for Restanza NDA". Drugs.com. Retrieved 2014-03-26.

Further reading

• Interaction of the New Ketolide ABT-773 (Cethromycin) with Human Polymorphonuclear Neutrophils and the Phagocytic Cell Line PLB-985 In Vitro. 2004