Single-dose pharmacokinetics of daptomycin in children with suspected or proved gram-positive infections.

Author(s): Abdel-Rahman SM, Benziger DP, Jacobs RF, Jafri HS, Hong EF, Kearns GL

Affiliation(s): Division of Pediatric Clinical Pharmacology and Medical Toxicology, The Children's Mercy Hospital, University of Missouri, Kansas City, MO 64108, USA.

Publication date & source: 2008-04, Pediatr Infect Dis J., 27(4):330-4.

Publication type: Clinical Trial; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

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.