Single-dose pharmacokinetics of daptomycin in children with suspected or proved gram-positive infections.
BACKGROUND
New antimicrobials such as daptomycin fill a void in the growing need for antibiotics effective against resistant Gram-positive pathogens. Although the pharmacokinetics of daptomycin have been well characterized in adults, no studies have evaluated the pharmacokinetics and tolerability in a pediatric population.


METHODS
Twenty-five children (12-17 years, n = 8; 7-11 years, n = 8; 2-6 years, n = 9) were enrolled in this multicenter, open-label study. Daptomycin was administered as a single 4-mg/kg intravenous dose followed by repeated blood sampling for 24 hours. Daptomycin was quantitated from plasma using a validated high performance liquid chromatography method and pharmacokinetic variables determined using a model-dependent approach.


RESULTS
Daptomycin systemic exposure decreased with decreasing age, reflecting more rapid rates of clearance in younger children. Total body exposure estimates in adolescents were approximately 1.7x those observed in children <6 years of age (374.4 versus 215.3 microg*h/L), they were comparable to those observed in adult historic controls. Estimates of apparent elimination half-life averaged 6.7 hours in adolescents, 5.6 hours in children 7-11 years of age, and 5.3 hours in children <6 years of age. One child had an adverse event (infusion site reaction) considered to be related to study drug.


CONCLUSIONS
Systemic drug exposure after a single weight-adjusted daptomycin dose is reduced in younger children compared with adolescents and adults consequent to an apparent age-associated change in total plasma clearance.
Abdel-Rahman
Susan M
SM
Division of Pediatric Clinical Pharmacology and Medical Toxicology, The Children's Mercy Hospital, University of Missouri, Kansas City, MO 64108, USA.
Benziger
David P
DP
Jacobs
Richard F
RF
Jafri
Hasan S
HS
Hong
Erica Fischer
EF
Kearns
Gregory L
GL
D000293:Adolescent; D000367:Age Factors; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D017576:Daptomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010949:Plasma / Q000737:chemistry
D000900:Anti-Bacterial Agents; D017576:Daptomycin