Pharmacokinetic‐Pharmacodynamic Considerations in the Design of Hospital‐Acquired or Ventilator‐Associated Bacterial Pneumonia Studies: Look before You Leap!
- 1 August 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 51 (S1), S103-S110
- https://doi.org/10.1086/653057
Abstract
Our thesis is a simple one: although a drug can fail in an individual patient for many reasons, appropriately sized and conducted drug-development programs often fail because of insensitive, uninformative end points, and/or poor a priori regimen decisions. The difficulty in successfully developing antimicrobial agents at present is often exacerbated by company decision-makers who are either uninformed or disregard the difference between empirical-based (ie, akin to playing pin-the-tail on the donkey) and quantitative model-based development plans. Frequently, the focus is on Gantt charts (project event schedules) and the on-time submission of a New Drug Application to a regulatory body, such as the US Food and Drug Administration. Suchmisplaced focus has led and will continue to lead to a number of problems, including program failure or, even worse, regulatory approval of an inappropriate dosing regimen with associated negative safety and efficacy sequelae. We believe that the goal of drug development is not a New Drug Application submitted on time but, rather, an approved, differentiated, safe, and effective new medicine. Here, we focus on the pharmacokinetic-pharmacodynamic data needed to guide dosing regimen decisions for patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia. Early consideration of these data in development programs will reduce risk not only to sponsors but also, most importantly, to the patients enrolled in the clinical trials.Keywords
This publication has 10 references indexed in Scilit:
- Microbial Etiologies of Hospital‐Acquired Bacterial Pneumonia and Ventilator‐Associated Bacterial PneumoniaClinical Infectious Diseases, 2010
- Identifying Exposure Targets for Treatment of Staphylococcal Pneumonia with CeftobiproleAntimicrobial Agents and Chemotherapy, 2009
- Exposure-Response Analyses of Tigecycline Efficacy in Patients with Complicated Intra-Abdominal InfectionsAntimicrobial Agents and Chemotherapy, 2008
- Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining FluidAntimicrobial Agents and Chemotherapy, 2008
- Evaluation of Tigecycline Penetration into Colon Wall Tissue and Epithelial Lining Fluid Using a Population Pharmacokinetic Model and Monte Carlo SimulationAntimicrobial Agents and Chemotherapy, 2007
- The Relationship between Quinolone Exposures and Resistance Amplification Is Characterized by an Inverted U: a New Paradigm for Optimizing Pharmacodynamics To Counterselect ResistanceAntimicrobial Agents and Chemotherapy, 2007
- Pharmacokinetics and lung concentrations of ertapenem in patients with ventilator-associated pneumoniaIntensive Care Medicine, 2006
- Plasma and lung concentrations of ceftazidime administered in continuous infusion to critically ill patients with severe nosocomial pneumoniaIntensive Care Medicine, 2004
- Steady-state plasma and intrapulmonary concentrations of cefepime administered in continuous infusion in critically ill patients with severe nosocomial pneumonia*Critical Care Medicine, 2003
- Intrapulmonary penetration of linezolidJournal of Antimicrobial Chemotherapy, 2003