Comparative Antimicrobial Activity and Kill-Curve Investigations of Novel Ketolide Antimicrobial Agents (HMR 3004 and HMR 3647) Tested against Haemophilus influenzae and Moraxella catarrhalis Strains

111

Telithromycin (HMR 3647) is a novel ketolide antimicrobial with good activity against both common and atypical respiratory pathogens, including many resistant strains. This randomized, three-period crossover study determined the dose proportionality of telithromycin pharmacokinetics after single and multiple dosing in healthy subjects. In each treatment period, subjects received a single oral dose of 400, 800 or 1,600 mg of telithromycin followed 4 days later by the same dose once daily for 7 days. Blood and urine samples were taken throughout the study for determination of pharmacokinetic parameters for telithromycin and RU 76363, its main metabolite. Telithromycin and RU 76363 achieved steady state within 2 to 3 days of once-daily dosing. A slight accumulation of telithromycin was observed after 7 days of therapy, with values of the area under the concentration-time curve from 0 to 24 h approximately 1.5 times higher than those achieved with the single dose. The pharmacokinetics of telithromycin and RU 76363 deviated moderately from dose proportionality. At a dose of 800 mg/day, telithromycin attained mean maximal and trough plasma concentrations of 2.27 and 0.070 mg/liter respectively. Elimination was biphasic; initial and terminal half-lives were 2.87 and 9.81 h for the 800-mg dose. Study medication was well tolerated, although adverse events tended to be more frequent at the 1,600-mg dose. This study showed that telithromycin was generally well tolerated and suggests that a once-daily 800-mg oral dose of telithromycin maintains an effective concentration in plasma for the treatment of respiratory tract infections involving the key respiratory pathogens.

mentioning

confidence: 99%

Pharmacokinetics of the New Ketolide Telithromycin (HMR 3647) Administered in Ascending Single and Multiple Doses

Namour¹,

Wessels²,

Pascual³

et al. 2001

111

“…Telithromycin, a new ketolide antimicrobial agent, has sufficient potency, with an antibacterial spectrum that covers all major respiratory tract pathogens, against isolates from respiratory tract infections (RTIs) and exhibits potent antibacterial activity against gram-positive aerobes, including Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus, fastidious gram-negative bacilli, including Haemophilus influenzae and Moraxella catarrhalis, intracellular pathogens, including Chlamydia pneumoniae, Legionella pneumophila, and atypical microorganisms, such as Mycoplasma pneumoniae (2,3,5,21). Unlike 14-and 15-available-membered-ring macrolides, telithromycin does not induce resistance to macrolides, lincosamide, or streptogramin B. Telithromycin retains antibacterial activity against most erythromycin A-resistant isolates within the gram-positive cocci, especially against S. pneumoniae.…”

mentioning

confidence: 99%

Intrapulmonary Pharmacokinetics of Telithromycin, a New Ketolide, in Healthy Japanese Volunteers

Kadota

Ishimatsu

Iwashita

et al. 2002

The concentrations of telithromycin, a new ketolide antimicrobial agent, in alveolar macrophages (AMs) and bronchoalveolar epithelial lining fluid (ELF) were determined in order to investigate the transfer of the drug into target tissue, relative to plasma, following multiple oral doses of telithromycin. Twenty-four healthy male Japanese volunteers were randomly allocated to four groups. Each subject was given 600 or 800 mg of telithromycin once daily for 5 days, followed by bronchoalveolar lavage (

“…Many reports indicate that telithromycin has potent antibacterial activity against 14-and 15-member macrolide-and/or penicillin G-resistant Streptococcus pneumoniae (1,8). It was also reported that the in vitro activity of telithromycin against Haemophilus influenzae is comparable to that of azithromycin and greater than that of clarithromycin (1,2).…”

mentioning

confidence: 99%

In Vivo Efficacy of Telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae

Okamoto

Miyazaki

Tateda

et al. 2001