Population Pharmacokinetics of Intraventricular Vancomycin in Neonatal Ventriculitis, A Preterm Pilot Study
| Autor: | Jaya Madhura Parasuraman, Frank Kloprogge, Joseph F. Standing, Axel Heep, Mahableshwar Albur |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
neonatal ventriculitis
Population Pharmaceutical Science Pilot Projects 02 engineering and technology 030226 pharmacology & pharmacy Article Cerebral Ventriculitis 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Vancomycin Ventriculitis Humans Medicine cardiovascular diseases Prospective Studies Dosing Prospective cohort study education CSF albumin education.field_of_study business.industry Infant Newborn Area under the curve Infant biochemical phenomena metabolism and nutrition 021001 nanoscience & nanotechnology medicine.disease intraventricular vancomycin nervous system diseases Anti-Bacterial Agents preterm pharmacokinetics Anesthesia NONMEM modelling 0210 nano-technology business Infant Premature medicine.drug |
| Zdroj: | European Journal of Pharmaceutical Sciences |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2020.105643 |
| Popis: | Highlights • Pharmacokinetics modelling of intraventricular vancomycin in a preterm pilot study. • Intraventricular vancomycin follows a one compartment model in neonatal ventriculitis treatment. • Ventricular Index, a dosing parameter, does not influence cerebrospinal fluid vancomycin levels. Aim Intraventricular vancomycin is an effective treatment for neonatal ventriculitis, as the cerebrospinal fluid (CSF) vancomycin levels reach adequate concentrations to achieve microbiological cure. There is no robust data on intraventricular vancomycin pharmacokinetics in the preterm population. This pilot population pharmacokinetic modelling study examines the pharmacokinetic behaviour of intraventricular vancomycin in the preterm population of < 28 weeks gestation, to inform the feasibility of future prospective studies. Methods The study comprised 8 preterm infants with neonatal ventriculitis (median gestation age 25.3 weeks; range 23.9 - 27.7). Population pharmacokinetics (non-linear mixed effects modelling) were described with one- and two-compartment models to fit plasma concentrations of vancomycin. A CSF compartment was added to the plasma modelling and mass transfer examined. Three covariates (serum creatinine, ventricular index (VI) and CSF protein) were tested on the final model. Area under the curve (AUC) and average CSF concentration (C average) predictions were generated from the final model and compared with time to microbiological cure. Results A one-compartment model provided the best fit to the data. There was no appreciable transfer between plasma and CSF. None of the covariates provided a significant reduction in the objective function value (OFV). Generally, time to sterilisation with higher CSF AUC (0-24) and C average tends to be shorter, however this should be interpreted with caution as data is erratic. Conclusion This pilot population pharmacokinetic analysis provides important information to warrant changes in the management of intraventricular vancomycin treatment in the preterm population, such as the current use of VI as a dosing parameter. Further study with a larger data pool is necessary to investigate the influence of VI on CSF vancomycin and ascertain dosing strategies. Graphical abstract Image, graphical abstract |
| Databáze: | OpenAIRE |
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