title: Application of pharmacokinetic-pharmacodynamic modeling and the justification of a novel fusidic acid dosing regimen: raising Lazarus from the dead.
abstract: Perhaps the most crucial step in the clinical development of an antimicrobial agent is the selection of a dosing regimen. Such decisions impact not only the success of a program but also the well being of individual patients, the emergence of resistance, and society as a whole. For fusidic acid, the selection of a dosing regimen for the treatment of patients with acute bacterial skin and skin-structure infection (ABSSSI) was based on the integration of knowledge gained from human population pharmacokinetic, in vitro infection, and mathematical models. The overarching goal of these studies was to identify a dosing regimen that would maximize the probabilities of positive clinical outcomes and limit the emergence of bacterial resistance during therapy. Novel dosing regimens identified included 1500 mg twice daily on day 1 followed by 600 mg twice daily for 10-14 days, a regimen that was subsequently found to be effective in a phase 2 clinical study of patients with ABSSSI. Herein, we review the data supporting the use of this novel fusidic acid dosing regimen, which will undergo further clinical evaluation in phase 3 clinical trials.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, New York, USA..
authors.forename: Brian T
authors.initials: BT
authors.lastname: Tsuji
authors.forename: Olanrewaju O
authors.initials: OO
authors.lastname: Okusanya
authors.forename: Jurgen B
authors.initials: JB
authors.lastname: Bulitta
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Sujata M
authors.initials: SM
authors.lastname: Bhavnani
authors.forename: Prabha B
authors.initials: PB
authors.lastname: Fernandez
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ambrose
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D015169:Colony Count, Microbial; D004334:Drug Administration Schedule; D005672:Fusidic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008954:Models, Biological; D009010:Monte Carlo Method; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013290:Streptococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005672:Fusidic Acid