Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis.
Pediatr Pulmonol
; 55(8): 2025-2032, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32421928
ABSTRACT
BACKGROUND:
The antipseudomonal cephalosporin/ß-lactamase inhibitor combination ceftolozane/tazobactam could be a potential treatment option for cystic fibrosis (CF) pulmonary exacerbations. The pharmacokinetics (PK) of ceftolozane/tazobactam in children with CF merits further evaluation.METHODS:
This is a retrospective subgroup analysis of a phase 1, noncomparative trial that characterized PK, safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients. This analysis compares ceftolozane and tazobactam plasma PK parameters, estimated from a population PK model, between patients with and without CF enrolled in that trial. Individual attainment of PK/pharmacodynamic (PD) targets of ceftolozane and tazobactam (free ceftolozane concentration >4 µg/mL for >30% and free tazobactam concentration >1 µg/mL for 20% of the dosing interval) in patients with and without CF were evaluated.RESULTS:
The study enrolled 18 patients aged greater than or equal to 2 to less than 18 years old, which included 9 with CF. Weight-normalized ceftolozane PK parameters were similar between patients with CF (clearance 0.16 L/h/kg, half-life 1.54 hours, volume of distribution 0.26 L/kg) and without CF (clearance 0.15 L/h/kg, half-life 1.62 hours, volume of distribution 0.26 L/kg), as were most weight-normalized tazobactam PK parameters. Weight-normalized tazobactam clearance was higher in patients with CF (0.73 L/h/kg) than patients without CF (0.42 L/h/kg). All patients achieved the prespecified PK/PD targets for ceftolozane and tazobactam.CONCLUSIONS:
This retrospective analysis demonstrated generally similar weight-normalized plasma PK parameters for ceftolozane and tazobactam among children with and without CF; thus, projected doses for treatment of pediatric hospital-acquired/ventilator-associated pneumonia, which are higher than the pediatric complicated urinary tract infection/intra-abdominal infection doses, may be appropriate for treatment of CF pulmonary exacerbation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cefalosporinas
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Infecções por Bactérias Gram-Negativas
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Fibrose Cística
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Tazobactam
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Antibacterianos
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Pediatr Pulmonol
Ano de publicação:
2020
Tipo de documento:
Article