Telithromycin
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| Clinical data | |
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| Trade names | Ketek |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a604026 |
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| Routes of administration |
Oral |
| ATC code | |
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| Pharmacokinetic data | |
| Bioavailability | 57% |
| Protein binding | 60% to 70% |
| Metabolism | Hepatic (50% CYP3A4-mediated) |
| Biological half-life | 10 hours |
| Excretion | Biliary and renal |
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| ChEMBL | |
| ECHA InfoCard | 100.208.206 |
| Chemical and physical data | |
| Formula | C43H65N5O10 |
| Molar mass | 812.004 g/mol |
| 3D model (Jmol) | |
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Telithromycin is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek. It is used to treat community acquired pneumonia of mild to moderate severity. After significant safety concerns, the US Food and Drug Administration sharply curtailed the approved uses of the drug in early 2007.
Telithromycin is a semi-synthetic erythromycin derivative. It is created by substituting a ketogroup for the cladinose sugar and adding a carbamate ring in the lactone ring. An alkyl-aryl moiety is attached to this carbamate ring. Furthermore, the carbon at position 6 has been methylated, as is the case in clarithromycin, to achieve better acid-stability.
French pharmaceutical company Hoechst Marion Roussel (later Sanofi-Aventis) began phase II/III clinical trials of telithromycin (HMR-3647) in 1998. Telithromycin was approved by the European Commission in July 2001 and subsequently went on sale in October 2001. In the US, telithromycin received U.S. Food and Drug Administration (FDA) approval on April 1, 2004.
FDA staffers publicly complained that safety problems and some data integrity issues were ignored prior to approval, and the House Committee on Energy and Commerce held hearings to examine these complaints. One doctor went to prison because she falsified data in her portion of the clinical trials (about 400 patients out of 24,000). Further, Ketek seemed to cause liver problems, including "liver failure", to a greater extent than would be expected of a common-use antibiotic. The House Committee on Energy and Commerce held hearings.
Study 3014 was a key clinical trial of approximately 24,000 patients which Sanofi-Aventis submitted to the FDA to seek approval for Ketek. The doctor who treated the most patients in Study 3014 (about 400), Maria "Anne" Kirkman Campbell, served a 57-month sentence in federal prison after pleading guilty to mail fraud, by defrauding Aventis and others. The indictment states that Campbell fabricated data she sent to the company. Documents, including internal Sanofi-Aventis emails show that Aventis was worried about Campbell early in study 3014 but didn't tell the FDA until the agency's own inspectors discovered the problem independently.
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