Pharmacokinetics and tolerability of single-dose intravenous ertapenem in infants, children, and adolescents.
BACKGROUND
Ertapenem is a carbapenem antibiotic with broad spectrum activity and a pharmacokinetic profile that favors once-daily administration in adults.


OBJECTIVE
This investigation was designed to evaluate the dose-exposure profile of ertapenem in children from infancy through adolescence.


METHODS
Eighty-four children (3 months-16 years) requiring antibiotic therapy were enrolled in this multicenter trial. Children received a single intravenous dose of ertapenem at 15, 20, or 40 mg/kg followed by repeated blood sampling for 24 hours. Free and total plasma ertapenem concentrations were quantitated by high-performance liquid chromatography, and the pharmacokinetics were determined using a model-independent approach.


RESULTS
Ertapenem exposure increased proportionally with increasing dose; however, achievable concentrations were influenced by age. Children older than 12 years attained higher dose-normalized concentrations at the end of the infusion (concentration at the end of the infusion [Ceoi]: 8.7 ± 1.9 mg/L per mg/kg dose) and total body exposure (area under the curve area under the plasma concentration-time curve [AUC]0-∞: 34.7 ± 14.7 mg hr/L per mg/kg dose) as compared with children 2 to 12 years (Ceoi: 6.9 ± 2.4 mg/L per mg/kg dose, AUC0-∞: 18.4 ± 8.0 mg hr/L per mg/kg dose) and children younger than 2 years (Ceoi: 6.1 ± 2.2 mg/L per mg/kg dose, AUC0-∞: 17.0 ± 5.4 mg hr/L per mg/kg dose). These findings were accounted for by age-dependent changes in ertapenem clearance and distribution volume. In 3 children adverse events (nausea, n = 2; injection site reaction, n = 1) were considered related to study drug administration.


CONCLUSIONS
Children younger than 12 years require dosing more frequently than once daily to achieve optimal efficacy when treating organisms with a minimum inhibitory concentration near the susceptibility breakpoint.
Abdel-Rahman
Susan M
SM
Division of Pediatric Clinical Pharmacology and Medical Toxicology, The Children's Mercy Hospital, Kansas City, MO, USA.
Kearns
Gregory L
GL
Topelberg
Santiago
S
Jacobs
Richard F
RF
Mistry
Goutam C
GC
Majumdar
Anup
A
Xu
Yang
Y
Wagner
John A
JA
Kitchen
Chester J
CJ
Groff
Michelle
M
Herman
Gary
G
Blumer
Jeffrey L
JL
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D000077727:Ertapenem; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010949:Plasma / Q000737:chemistry; D047090:beta-Lactams / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem