Efficacy, safety and pharmacokinetics of telithromycin in patients with respiratory tract infections

The efficacy, safety and pharmacokinetics of telithromycin (TEL), a new ketolide antibiotic, were evaluated by three clinical studies in patients with respiratory infections. The efficacy and safety in 7 days treatment duration with 600 mg once daily were assessed in the Phase II open label study (open study of 7 days). In the Phase II open label clinical pharmacology study (PK study), sputum concentrations of TEL in 7 days treatment duration with 600 mg once daily were determined periodically for 7 days and the propriety of TEL 600 mg treatment was primarily investigated. Furthermore, in the Phase III open label study (open study of 5 days) the treatment method was the same as in 7 days treatment but treatment duration period was shortened to 5 days, and the efficacy, safety and newly additional final assessment were investigated. 1. Clinical efficacy/final assessment The efficacy rates in 7 days-open study, pharmacology study and 5 days-open study were respectively 92.0% (23/25) , 6/7 and 92.7% (89/96). The final assessment in 5 days treatment study (treatment cure rate) was 85.6% (83/97). The clinical efficacy in 10 cases whose causative organism was judged as penicillin- or macrolide-resistant Streptococcus pneumoniae in 3 studies was every "effective". 2. Bacteriological efficacy. The eradication rates in 7 days-open study, pharmacology study and 5 days-open study were respectively 75.0% (6/8), 1/3 and 86.0% (37/43). 3. Pharmacokinetics. (PK) The maximum concentrations (mean values) of TEL in the spectrum and plasma were respectively 8.45 μg/mL and 1.78 μg/mL, and the mean transfer rate into sputum (the maximum sputum concentration/the maximum plasma concentration) was 4.75. 4. Safety. The incidence rates of side effects in 7 days and 5 days open studies were respectively 44.8% (13/29) and 34.5% (41/119). In the pharmacology study, there were no side effects. Side effects with relatively higher incidence rates were gastro-intestinal tract disturbances and hepato-biliary tract related disturbances. They were all mild to moderate and recovered or improved without any sequela. In there 3 studies, TEL was recognized to be highly effective against respiratory tract infections and to be well transferred into sputum. From above findings, it was suggested that TEL could exhibit sufficient usefulness with 600 mg once daily treatment for 5 days against respiratory tract infections.