Pharmacokinetic and Pharmacodynamic Target Attainment in Adult and Pediatric Patients Following Administration of Ceftaroline Fosamil as a 5‐Minute Infusion

Autor:	Phylinda L. S. Chan, Timothy J. Carrothers, William Knebel, Todd Riccobene, Susan Raber
Rok vydání:	2021
Předmět:	Adult Male Adolescent medicine.drug_class Antibiotics Population Cmax Pharmaceutical Science Microbial Sensitivity Tests Pharmacology Models Biological 030226 pharmacology & pharmacy 03 medical and health sciences Minimum inhibitory concentration 0302 clinical medicine Pharmacokinetics population pharmacokinetics infusion duration Humans ceftaroline fosamil Medicine Ceftaroline fosamil Computer Simulation Pharmacology (medical) Renal Insufficiency Child Infusions Intravenous education PK/PD models education.field_of_study business.industry Brief Report Age Factors PK/PD Infant Anti-Bacterial Agents Cephalosporins probability of target attainment Area Under Curve Child Preschool 030220 oncology & carcinogenesis Pharmacodynamics Female business medicine.drug
Zdroj:	Clinical Pharmacology in Drug Development
ISSN:	2160-7648 2160-763X
DOI:	10.1002/cpdd.907
Popis:	The key pharmacokinetic/pharmacodynamic (PK/PD) efficacy index for β‐lactam antibiotics is the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (MIC) of bacteria during each dosing interval (fT>MIC). Ceftaroline fosamil, the prodrug of the β‐lactam ceftaroline, was initially approved for administration as 60‐minute intravenous (IV) infusions. Population PK analyses comparing exposure and PK/PD target attainment for 5‐minute and 60‐minute IV infusions, described here, have supported ceftaroline fosamil labeling updates to include variable infusion durations of 5 to 60 minutes in adults and children aged ≥2 months. A 2‐compartment disposition PK model for ceftaroline fosamil and ceftaroline was used to predict steady‐state ceftaroline exposures (maximum plasma concentrations [Cmax,ss] and area under the plasma concentration–time curve over 24 hours [AUCss,0‐24]) and probability of target attainment in simulated adult and pediatric patients with various degrees of renal function receiving standard doses of ceftaroline fosamil as 5‐minute or 60‐minute IV infusions. Across age groups and renal function categories, median ceftaroline AUCss,0‐24 values were similar for 5‐minute and 60‐minute infusions, whereas Cmax,ss was up to 42% higher for 5‐minute infusions. Both infusion durations achieved >99% probability of target attainment based on PK/PD targets for Staphylococcus aureus (35% fT>MIC) and Streptococcus pneumoniae (44% fT>MIC) at European Committee on Antimicrobial Susceptibility Testing/Clinical and Laboratory Standards Institute MIC breakpoints (1 mg/L and 0.25/0.5 mg/L, respectively). These findings support administration of standard ceftaroline fosamil doses over 5 to 60 minutes for adults and children aged ≥2 months, providing added flexibility to clinicians and patients.
Databáze:	OpenAIRE
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