Pharmacokinetic-pharmacodynamic Modeling to Support Doripenem Dose Regimen Optimization for Critically Ill Patients

Diagn Microbiol Infect Dis. 2009 Apr;63(4):409-14. doi: 10.1016/j.diagmicrobio.2009.01.027. Epub 2009 Feb 26.

Abstract

Dose regimen selection in late-phase clinical trials is critical for successful drug development, the well-being of individual patients, and given the ongoing emergence of antimicrobial resistance, society as a whole. Herein we describe some of the animal pharmacokinetics-pharmacodynamics, human pharmacokinetic, and in silico modeling work that was conducted in an effort to maximize the probability of a positive clinical response to therapy and minimize the likelihood for exposure-related toxicity for doripenem in phase 3 clinical studies. Some of the dosing regimens identified have been validated as effective in phase 3 clinical studies (500 mg infused over 1 h every 8 h for complicated intra-abdominal infections), whereas others (1000 mg infused over 4 h every 8 h for hospital-acquired pneumonia) are undergoing clinical evaluation.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Bacterial Infections / drug therapy*
  • Carbapenems / administration & dosage*
  • Carbapenems / pharmacokinetics*
  • Clinical Trials as Topic
  • Computer Simulation
  • Critical Illness*
  • Doripenem
  • Female
  • Humans
  • Mice

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Doripenem