Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens

Autor: Charles Burdet, Laurence Armand-Lefevre, Michel Wolff, L. Massias, Cédric Laouénan, Camille Couffignal, Olivier Pajot, Arnaud Foucrier
Přispěvatelé: Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Unité de soins intensifs [Dupouy], Centre Hospitalier Victor Dupouy, Unité de Soins Intensifs et de Maladies Infectieuses, Pharmacie, This study was funded by the Contrat d’Initiation à la Recherche Clinique 2006 (Assistance Publique-Hôpitaux de Paris, Département de la Recherche Clinique et du Développement, CRC 06049)
Rok vydání: 2014
Předmět:
Imipenem
Population
Renal function
MESH: Pneumonia
Ventilator-Associated
MESH: Monte Carlo Method
MESH: Dose-Response Relationship
Drug
law.invention
ventilator-associated pneumonia
MESH: Aged
80 and over
Pharmacokinetics
population pharmacokinetics
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
law
MESH: Anti-Bacterial Agents
MESH: Gram-Negative Bacteria
Medicine
Pharmacology (medical)
MESH: Infusions
Intravenous
education
MESH: Aged
MESH: Imipenem
Pharmacology
education.field_of_study
MESH: Middle Aged
MESH: Humans
business.industry
MESH: Models
Biological
Ventilator-associated pneumonia
MESH: Adult
[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
medicine.disease
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Intensive care unit
MESH: Male
MESH: Prospective Studies
3. Good health
critical care
Regimen
Anesthesia
Pharmacodynamics
MESH: Critical Illness
business
MESH: Female
MESH: Models
Statistical
imipenem
medicine.drug
Zdroj: British Journal of Clinical Pharmacology
British Journal of Clinical Pharmacology, Wiley, 2014, 78 (5), pp.1022-34. ⟨10.1111/bcp.12435⟩
ISSN: 0306-5251
1365-2125
Popis: International audience; Significant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator-associated pneumonia and evaluate several dosage regimens. This French multicentre, prospective, open-label study was conducted in ICU patients with a presumptive diagnosis of ventilator-associated pneumonia caused by Gram-negative bacilli, who empirically received imipenem intravenously every 8 h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%. Fifty-one patients were included in the PK analysis. Imipenem concentration data were best described by a two-compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between-subject variability) was 13.2 l h(-1) (38%) and estimated central volume 20.4 l (31%). At an MIC of 4 μg ml(-1) , the probability of achieving 40% fractional time > MIC was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h and 96.9% for 1000 mg every 6 h. This population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not 1000 mg every 8 h.
Databáze: OpenAIRE
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