Pharmacokinetics and comparative effects of telithromycin (HMR 3647) and clarithromycin on the oropharyngeal and intestinal microflora

The pharmacokinetics in plasma and saliva of a new ketolide, telithromycin (HMR 3647), and the effect on the normal oropharyngeal and intestinal micro flora were studied in healthy volunteers and compared with those of clarith romycin. Ten subjects received 800 mg telithromycin perorally once daily an d 10 other subjects received 500 mg clarithromycin bid for 10 days. Blood, saliva and faecal specimens were collected at defined intervals before, dur ing and after administration for pharmacokinetic and microbiological analys es. In subjects receiving telithromycin, the mean C-max, AUC and C-24 (24 h ) in saliva exceeded the values obtained from plasma, while saliva and seru m pharmacokinetic parameters were in the same range for the clarithromycin group. The quantitative ecological disturbances in the normal microflora du ring administration of telithromycin were moderate and comparable to those associated with clarithromycin administration. No overgrowth of yeasts or C lostridium difficile occurred. Emergence of resistant strains was seen in b oth treatment groups. Administration of both telithromycin and clarithromyc in was associated with significant increases in MICs for intestinal Bactero ides isolates, which persisted 2 weeks after discontinuation of treatment. In addition, a significant emergence of highly clarithromycin-resistant a-h aemolytic streptococci, intestinal enterococci and Enterobacteriaceae was d etected at day 10 in the clarithromycin group. In conclusion, administratio n of telithromycin resulted in high drug levels in saliva, which indicates a good therapeutic profile for throat infections. Telithromycin seems to ha ve a more favourable ecological profile compared with clarithromycin in ter ms of resistance development in the normal microflora.