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Antimicrobial Agents and Chemotherapy, January 2008, p. 92-97, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00875-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Intrapulmonary Distribution of Intravenous Telavancin in Healthy Subjects and Effect of Pulmonary Surfactant on In Vitro Activities of Telavancin and Other Antibiotics{triangledown}

Mark H. Gotfried,1,2 Jeng-Pyng Shaw,3 Bret M. Benton,3 Kevin M. Krause,3 Michael R. Goldberg,3 Michael M. Kitt,3 and Steven L. Barriere3*

School of Medicine, University of Arizona, Pulmonary Associates, Phoenix, Arizona,1 Department of Pharmacy Practice, College of Pharmacy, University of Illinois, Chicago, Illinois,2 Theravance, Inc., South San Francisco, California3

Received 4 July 2007/ Returned for modification 27 July 2007/ Accepted 27 September 2007

Steady-state concentrations of telavancin, a novel, bactericidal lipoglycopeptide, were determined in the plasma, pulmonary epithelial lining fluid (ELF), and alveolar macrophages (AMs) of 20 healthy subjects. Telavancin at 10 mg of drug/kg of body weight/day was administered as a 1-h intravenous infusion on three successive days, with bronchoalveolar lavage performed on five subjects, each at 4, 8, 12, and 24 h after the last dose. Plasma samples were collected before the first and third infusions and at 1, 2, 3, 4, 8, 12, and 24 h after the third infusion. The plasma telavancin concentration-time profile was as reported previously. Telavancin (mean ± standard deviation) penetrated well into ELF (3.73 ± 1.28 µg/ml at 8 h and 0.89 ± 1.03 µg/ml at 24 h) and extensively into AMs (19.0 ± 16.8 µg/ml at 8 h, 45.0 ± 22.4 µg/ml at 12 h, and 42.0 ± 31.4 µg/ml at 24 h). Mean concentrations in AMs and plasma at 12 h were 45.0 µg/ml and 22.9 µg/ml (mean AM/plasma ratio, 1.93), respectively, and at 24 h were 42.0 µg/ml and 7.28 µg/ml (mean AM/plasma ratio, 6.67), respectively. Over the entire dosing interval, telavancin was present in ELF and AMs at concentrations up to 8-fold and 85-fold, respectively, above its MIC90 for methicillin-resistant Staphylococcus aureus (0.5 µg/ml). Pulmonary surfactant did not affect telavancin's in vitro antibacterial activity. Telavancin was well tolerated. These results support the proposal for further clinical evaluation of telavancin for treating gram-positive respiratory infections.

* Corresponding author. Mailing address: Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080. Phone: (650) 808-6025. Fax: (650) 808-6441. E-mail: sbarriere{at}theravance.com

{triangledown} Published ahead of print on 8 October 2007.

Antimicrobial Agents and Chemotherapy, January 2008, p. 92-97, Vol. 52, No. 1
0066-4804/08/$08.00+0     doi:10.1128/AAC.00875-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Charneski, L., Patel, P. N, Sym, D. (2009). Telavancin: A Novel Lipoglycopeptide Antibiotic. The Annals of Pharmacotherapy 43: 928-938 [Abstract] [Full Text]  
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  • Yin, L.-Y., Calhoun, J. H., Thomas, T. S., Wirtz, E. D. (2009). Efficacy of telavancin in the treatment of methicillin-resistant Staphylococcus aureus osteomyelitis: studies with a rabbit model. J Antimicrob Chemother 63: 357-360 [Abstract] [Full Text]  
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