3578 Telithromycin Telithromycin, a semi-synthetic erythromycin derivative, belongs to a new chemical class of antibiotics called ketolides. Ketolides have been recently added to the macrolide-lincosamide-streptogramin class of antibiotics. Similar to the macrolide antibiotics, telithromycin prevents bacterial growth by interfering with bacterial protein synthesis. Telithromycin binds to the 50S subunit of the 70S bacterial ribosome and blocks further peptide elongation. Binding occurs simultaneously at to two domains of 23S RNA of the 50S ribosomal subunit, domain II and V, where older macrolides bind only to one. It is used to treat mild to moderate respiratory infections. 191114-48-4 5462516 C43H65N5O10 811.473140 White powder. 176-188°C 300 mg/L Absolute bioavailability is approximately 57%. Maximal concentrations are reached 0.5 - 4 hours following oral administration. Food intake does not affected absorption. Telithromycin acts by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding at domain II, telithromycin retains activity against gram-positive cocci (e.g., <i>Streptococcus pneumoniae</i>) in the presence of resistance mediated by methylases (erm genes) that alter the domain V binding site of telithromycin. Telithromycin may also inhibit the assembly of nascent ribosomal units. Compared to erythromycin A, telithromycin binds to the 23S rRNA with 10 times greater affinity in erythromycin-susceptible organisms and 25 times greater affinity in macrolide-resistant strains. This increased binding affinity may be conferred by the C11-12 carbamate side chain of telithromycin. The side chain appears to maintain binding at domain II in the presence of resistance mediated by alterations in domain V. Hepatic - estimated 50% metabolized by CYP3A4 and 50% metabolized independent of cytochrome P450 Route of Elimination: The systemically available telithromycin is eliminated by multiple pathways as follows: 7% of the dose is excreted unchanged in feces by biliary and/or intestinal secretion; 13% of the dose is excreted unchanged in urine by renal excretion; and 37% of the dose is metabolized by the liver. Half Life: Main elimination half-life is 2-3 hours; terminal elimination half-life is 10 hours LD50>2000 mg/kg (PO in rats). No indication of carcinogenicity to humans (not listed by IARC). For the treatment of <i>Pneumococcal</i> infection, acute sinusitis, acute bacterial tonsillitis, acute bronchitis and bronchiolitis, lower respiratory tract infection and lobar (pneumococcal) pneumonia. Most common side-effects are gastrointestinal, including diarrhea, nausea, abdominal pain and vomiting. Headache and disturbances in taste also occur. Less common side-effects include palpitations, blurred vision and rashes. [Wikipedia] 2009-07-30T17:59:10Z 2014-12-24T20:26:08Z Telithromycin C12009 Telithromycin DB00976 true [H][C@]12N(CCCCN3C=NC(=C3)C3=CN=CC=C3)C(=O)O[C@@]1(C)[C@]([H])(CC)OC(=O)[C@]([H])(C)C(=O)[C@]([H])(C)[C@@]([H])(O[C@]1([H])O[C@]([H])(C)C[C@]([H])(N(C)C)[C@@]1([H])O)[C@@](C)(C[C@@]([H])(C)C(=O)[C@]2([H])C)OC C43H65N5O10 InChI=1S/C43H65N5O10/c1-12-33-43(8)37(48(41(53)58-43)19-14-13-18-47-23-31(45-24-47)30-16-15-17-44-22-30)27(4)34(49)25(2)21-42(7,54-11)38(28(5)35(50)29(6)39(52)56-33)57-40-36(51)32(46(9)10)20-26(3)55-40/h15-17,22-29,32-33,36-38,40,51H,12-14,18-21H2,1-11H3/t25-,26-,27+,28+,29-,32+,33+,36-,37-,38-,40+,42-,43+/m1/s1 InChIKey=LJVAJPDWBABPEJ-RMNISARHSA-N 812.0037 811.473143325 Exogenous Solid 3 HMDB15111 CHEMBL1136 26329513 <p>Suhas Sohani, Mandar Deodhar, Nishant Patel, Manish Patel, Mahesh Davadra, Vinodhamar Kansal, &#8220;Process for the Preparation of Telithromycin.&#8221; U.S. Patent US20070260066, issued November 08, 2007.</p>