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Antimicrobial Agents and Chemotherapy, January 2001, p. 170-175, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.170-175.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

F. Namour,* D. H. Wessels, M. H. Pascual, D. Reynolds, E. Sultan, and B. Lenfant

Aventis Pharma, Hoechst Marion Roussel/Romaineville, 93235 Romainville Cedex, France

Received 27 April 2000/Returned for modification 31 July 2000/Accepted 17 October 2000

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.

* Corresponding author. Mailing address: Aventis Pharma, Hoechst Marion Roussel/Romaineville, 102 route de Noisy, 93235 Romainville Cedex, France. Phone: 33 1 4991 5807. Fax: 33 1 4991 4842. E-mail: florence.namour{at}aventis.com.

Antimicrobial Agents and Chemotherapy, January 2001, p. 170-175, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.170-175.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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