to one domain and weakly to the second domain. Like many other protein synthesis inhibitors, telithromycin can also inhibit the formation of ribosomal subunits 50S and 30S. Pharmacokinetics Unlike erythromycin, telithromycin is acid-stable and can therefore be taken orally while being protected from gastric acids. It is fairly rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, telithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of telithromycin is released. The concentration of telithromycin in the tissues is much higher than in plasma. Telithromycin fulfills a role that has arisen due to the rise of microbial resistance to existing macrolides and appears to be effective against macrolide-resistant Streptococcus pneumoniae. The defining differentiating characteristic of the ketolides as opposed to other macrolides is the removal of the neutral sugar, L-cladinose from the 3 position of the macrolide ring and the subsequent oxidation of the 3-hydroxyl to a 3-keto functional group. Metabolism Telithromycin is metabolized mainly in the liver, the main elimination route being the bile, a small portion is also excreted into the urine. About one third is excreted unchanged in bile and urine, the biliary route being favoured. Telithromycin's half-life is approximately ten hours. History 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. Safety controversies and fraud 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