An Evaluation of Vancomycin Area Under the Curve Estimation Methods for Children Treated for Acute Pulmonary Exacerbations of Cystic Fibrosis Due to Methicillin-ResistantStaphylococcus aureus
Autor: | David C. Young, Chris Stockmann, Jahidur Rashid, Kwabena Krow Ampofo, Lisa Lubsch, Adam Frymoyer, Jeffery T. Zobell, Catherine M.T. Sherwin, Jared K. Olson, Xiaoxi Liu, Yuhuan Wang, Adam L. Hersh |
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Rok vydání: | 2018 |
Předmět: |
Male
Methicillin-Resistant Staphylococcus aureus medicine.medical_specialty Adolescent Cystic Fibrosis Population medicine.disease_cause 030226 pharmacology & pharmacy Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Vancomycin Interquartile range Internal medicine medicine Humans Pharmacology (medical) Trough Concentration Dosing Child education Pharmacology education.field_of_study business.industry Area under the curve Methicillin-resistant Staphylococcus aureus Area Under Curve Child Preschool 030220 oncology & carcinogenesis Female business medicine.drug |
Zdroj: | The Journal of Clinical Pharmacology. 59:198-205 |
ISSN: | 0091-2700 |
Popis: | The prevalence of pulmonary methicillin-resistant Staphylococcus aureus infections in patients with cystic fibrosis (CF) has increased over the last 2 decades. Two concentrations-a postdistributive and a trough-are currently used to estimate the area under the curve (AUC) of vancomycin, an antibiotic routinely used to treat these infections, to achieve the target AUC/minimum inhibitory concentration of ≥400 mg·h/L in ensuring optimal dosing of this drug. This study evaluated precision and bias in estimating vancomycin AUCs obtained either from a population pharmacokinetic (PK) model by using a single trough concentration or from standard PK equation-based 2-point monitoring approach. AUCs were either obtained from a single trough concentration-fitted model or derived from a model fitted by 2 concentration points. Children ≥2 years of age with CF received intravenous vancomycin at 2 centers from June 2012 to December 2014. A population PK model was developed in Pmetrics to quantify the between-subject variability in vancomycin PK parameters, define the sources of PK variability, and leverage information from the population to improve individual AUC estimates. Twenty-three children with CF received 27 courses of vancomycin. The median age was 12.3 (interquartile range [IQR] 8.5-16.6) years. From the individual vancomycin PK parameter estimates from the population PK model, median AUC was 622 (IQR 529-680) mg·h/L. Values were not significantly different from the AUC calculated using the standard PK equation-based approach (median 616 [IQR 540-663] mg·h/L) (P = .89). A standard PK equation-based approach using 2 concentrations and a population PK model-based approach using a single trough concentration yielded unbiased and precise AUC estimates. Findings suggest that options exist to implement AUC-based pediatric vancomycin dosing in patients with CF. The findings of this study reveal that several excellent options exist for centers to implement AUC-based pediatric vancomycin dosing for patients with CF. |
Databáze: | OpenAIRE |
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