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Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents. Antimicrob Agents Chemother 2005 Nov;49(11):4536-45

Date

10/28/2005

Pubmed ID

16251293

Pubmed Central ID

PMC1280172

DOI

10.1128/AAC.49.11.4536-4545.2005

Scopus ID

2-s2.0-27644585388   186 Citations

Abstract

Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m2/day or 70 mg/m2/day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC(0-24)) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m2/day (maximum, 70 mg/day), the AUC(0-24) following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC(0-24) and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m2 daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at 1 mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m2/day provides a comparable exposure to that of adult patients treated with 50 mg/day.

Author List

Walsh TJ, Adamson PC, Seibel NL, Flynn PM, Neely MN, Schwartz C, Shad A, Kaplan SL, Roden MM, Stone JA, Miller A, Bradshaw SK, Li SX, Sable CA, Kartsonis NA

Author

Cindy L. Schwartz MD, MPH Chief, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Antifungal Agents
Body Surface Area
Child
Child, Preschool
Echinocandins
Female
Humans
Lipopeptides
Male
Peptides, Cyclic
jenkins-FCD Prod-461 7d7c6113fc1a2757d2947d29fae5861c878125ab