title: Pharmacokinetics and safety of caspofungin in older infants and toddlers.
abstract: Although information about the efficacy and safety experience with caspofungin at 50 mg/m(2) daily is available for children and adolescents, the dosing regimen in infants and toddlers 3 to 24 months of age has yet to be established. We studied the pharmacokinetics and safety of caspofungin at 50 mg/m(2) once daily in nine patients 10 to 22 months (median, 13 months) of age with fever and neutropenia who received caspofungin once daily for 2 to 21 (mean, 9.3) days. Plasma caspofungin concentrations were measured by high-performance liquid chromatography assay on days 1 and 4. On day 4, the area under the curve from 0 to 24 h (AUC(0-24)) was 130.3 microg-h/ml, the peak concentration (C(1)) was 17.2 microg/ml, and the trough concentration (C(24)) was 1.6 microg/ml. The day 4 geometric mean ratios (GMRs) and 90% confidence interval (CI) for these parameters in infants/toddlers relative to adults were 1.26 (1.06, 1.50), 1.83 (1.57, 2.14), and 0.81 (0.64, 1.04), respectively. Relative to children (2 to 11 years of age), the day 4 GMRs (and 90% CI) were 1.13 (0.89, 1.44), 1.10 (0.85, 1.42), and 1.12 (0.72, 1.76), respectively. The harmonic mean elimination phase t(1/2) in infants/toddlers (8.8 h) was reduced approximately 33% relative to adults (13.0 h) but was similar to that in children (8.2 h). Clinical adverse events occurred in seven patients (78%); none were considered drug related. Laboratory adverse events occurred in five patients (56%) and were considered drug related in three (33%). There were no infusion-related events or discontinuations due to toxicity. Caspofungin at 50 mg/m(2) daily was well tolerated in infants and toddlers; the AUC and caspofungin C(24) were generally comparable to those in adults receiving caspofungin at 50 mg daily.
authors.affiliation: Children's Hospital, Los Angeles, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Neely
authors.forename: Hasan S
authors.initials: HS
authors.lastname: Jafri
authors.forename: Nita
authors.initials: N
authors.lastname: Seibel
authors.forename: Katherine
authors.initials: K
authors.lastname: Knapp
authors.forename: Peter C
authors.initials: PC
authors.lastname: Adamson
authors.forename: Susan K
authors.initials: SK
authors.lastname: Bradshaw
authors.forename: Kim M
authors.initials: KM
authors.lastname: Strohmaier
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Sheng
authors.initials: S
authors.lastname: Bi
authors.forename: Marissa Fallon
authors.initials: MF
authors.lastname: Dockendorf
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stone
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kartsonis
mesh_terms: D000935:Antifungal Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077336:Caspofungin; D054714:Echinocandins / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D055666:Lipopeptides; D008297:Male
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin