Abstract | OBJECTIVE: DESIGN: Pharmacokinetic analysis of Phase III Trial data. SETTING: PATIENTS: INTERVENTIONS: Serial blood samples were taken on day 2 or 3 of treatment and used for population pharmacokinetic analysis with nonlinear mixed effects modelling and Monte Carlo simulation. MEASUREMENTS AND MAIN RESULTS: A two-compartment linear model was most appropriate. The mean values for doripenem clearance (20.4 ± 14.2 L/hr) and volume of distribution (45.9 ± 36.3 L) were larger than that observed in previous studies in noncritically ill patients. Doripenem clearance was correlated with creatinine clearance and peripheral volume of distribution with patient body weight. Administration by extended infusion negated much of the pharmacokinetic variability caused by different patient body weight and renal function and enabled achievement of concentrations associated with maximal bacterial killing. CONCLUSION: : This is the first article describing the pharmacokinetics/pharmacodynamics of doripenem solely in critically ill patients and emphasizes the effect of patient weight and creatinine clearance on pharmacokinetics. Use of extended infusions with this antibiotic should be encouraged as it maximizes the likelihood of achieving target blood concentrations.
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Authors | Jason A Roberts, Jeffrey Lipman |
Journal | Critical care medicine
(Crit Care Med)
Vol. 41
Issue 2
Pg. 489-95
(Feb 2013)
ISSN: 1530-0293 [Electronic] United States |
PMID | 23263583
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Carbapenems
- Creatinine
- Doripenem
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Topics |
- Anti-Bacterial Agents
(administration & dosage, blood, pharmacokinetics)
- Carbapenems
(administration & dosage, blood, pharmacokinetics)
- Creatinine
(analysis)
- Critical Illness
(therapy)
- Cross Infection
(drug therapy)
- Doripenem
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Female
- Humans
- Intensive Care Units
- Male
- Middle Aged
- Monte Carlo Method
- Obesity
(epidemiology)
- Pneumonia, Bacterial
(drug therapy)
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