Dosing strategies of imipenem in neonates based on pharmacometric modelling and simulation
| Autor: | Eric Giannoni, Monia Guidi, Laurent A. Decosterd, Kim Dao, Chantal Csajka, Pascal André, Nicolas Widmer, Thierry Buclin, Sandra A. Asner, O. Marchetti, Marc Pfister, Aline Fuchs |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
medicine.medical_specialty Imipenem Critical Illness Population Gestational Age Gastroenterology chemistry.chemical_compound Internal medicine medicine Humans Pharmacology (medical) Computer Simulation Dosing education Antibacterial agent Pharmacology Volume of distribution education.field_of_study Creatinine business.industry Infant Newborn Gestational age Infant Anti-Bacterial Agents NONMEM Infectious Diseases chemistry business medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy, vol. 77, no. 2, pp. 457-465 |
| ISSN: | 1460-2091 |
| Popis: | Objectives Imipenem is a broad-spectrum antibacterial agent used in critically ill neonates after failure of first-line treatments. Few studies have described imipenem disposition in this population. The objectives of our study were: (i) to characterize imipenem population pharmacokinetics (PK) in a cohort of neonates; and (ii) to conduct model-based simulations to evaluate the performance of six different dosing regimens aiming at optimizing PK target attainment. Methods A total of 173 plasma samples from 82 neonates were collected over 15 years at the Lausanne University Hospital, Switzerland. The majority of study subjects were preterm neonates with a median gestational age (GA) of 27 weeks (range: 24–41), a postnatal age (PNA) of 21 days (2–153) and a body weight (BW) of 1.16 kg (0.5–4.1). PK data were analysed using non-linear mixed-effect modelling (NONMEM). Results A one-compartment model best characterized imipenem disposition. Population PK parameters estimates of CL and volume of distribution were 0.21 L/h and 0.73 L, with an interpatient variability (CV%) of 20.1% on CL in a representative neonate (GA 27 weeks, PNA 21 days, BW 1.16 kg, serum creatinine, SCr 46.6 μmol/L). GA and PNA exhibited the greatest impact on PK parameters, followed by SCr. These covariates explained 36% and 15% of interindividual variability in CL, respectively. Simulated regimens using a dose of 20–25 mg/kg every 6–12 h according to postnatal age led to the highest PTA (T>MIC over 100% of time). Conclusions Dosing adjustment according to BW, GA and PNA optimizes imipenem exposure in neonates. |
| Databáze: | OpenAIRE |
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