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.

Trial registration: ClinicalTrials.gov NCT00292071.

Figures

FIG. 1.

Mean plasma caspofungin concentrations in infants/toddlers (10 to 24 months), children (2 to 11 years), and adolescents (12 to 17 years) receiving caspofungin at 50 mg/m2 once daily and adults receiving caspofungin at 50 mg once daily.