J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
0091270008321273v1
48/9/1063    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dowell, J. A.
Right arrow Articles by Damle, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dowell, J. A.
Right arrow Articles by Damle, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

QUANTITATIVE CLINICAL PHARMACOLOGY

Pharmacokinetic-Pharmacodynamic Modeling of Dalbavancin, a Novel Glycopeptide Antibiotic

James A. Dowell, PhD, Beth P. Goldstein, PhD, Mary Buckwalter, MS, Martin Stogniew, PhD and Bharat Damle, PhD

From Vicuron Pharmaceuticals, a wholly owned subsidiary of Pfizer, Inc, and Pfizer, Inc, New York. Dr. James Dowell is a member of the American College of Clinical Pharmacology.

Dalbavancin is a novel glycopeptide with a 2-dose, once-weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for dalbavancin using population pharmacokinetic data and minimum inhibitory concentrations (MICs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t > MIC). The concentration-dependent target was an area under the concentration-time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was ≤0.5 µg/mL using AUC14 days/MIC and ≤1 µg/mL using t > MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 µg/mL. Because dalbavancin MIC90s for these species are well below these values, the analysis supports the use of once-weekly dosing regimens of dalbavancin in the treatment of complicated skin and skin structure infections.

Key Words: Dalbavancin • Monte Carlo simulations • pharmacodynamics • pharmacokinetics • susceptibility

Address for reprints: Bharat Damle, PhD, Director, Clinical Pharmacology, Pfizer Global Research and Development, 685 3rd Avenue, New York, NY 10017; e-mail: bharat.damle{at}pfizer.com.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American College of Clinical Pharmacology