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Pharmacokinetic‐Pharmacodynamic Modeling of Dalbavancin, a Novel Glycopeptide Antibiotic
Author(s) -
Dowell James A.,
Goldstein Beth P.,
Buckwalter Mary,
Stogniew Martin,
Damle Bharat
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008321273
Subject(s) - dalbavancin , teicoplanin , minimum inhibitory concentration , pharmacokinetics , pharmacodynamics , pharmacology , population , antibiotics , medicine , microbiology and biotechnology , dosing , glycopeptide , staphylococcus aureus , vancomycin , biology , bacteria , environmental health , genetics
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 Streptococcussp . These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was ≤0.5 μg/mL using AUC 14 days /MIC and ≤1 μg/mL using t > MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 μg/mL. Because dalbavancin MIC 90 s 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.