Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents.
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.
Walsh
Thomas J
TJ
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bldg. 10-CRC, Room 1W-5750, 10 Center Drive, Bethesda, Maryland 20892, USA. walsht@mail.nih.gov
Adamson
Peter C
PC
Seibel
Nita L
NL
Flynn
Patricia M
PM
Neely
Michael N
MN
Schwartz
Cindy
C
Shad
Aziza
A
Kaplan
Sheldon L
SL
Roden
Maureen M
MM
Stone
Julie A
JA
Miller
Alisha
A
Bradshaw
Susan K
SK
Li
Susan X
SX
Sable
Carole A
CA
Kartsonis
Nicholas A
NA
D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001830:Body Surface Area; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D054714:Echinocandins; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D000077336:Caspofungin