This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Neely, M.
Right arrow Articles by Kartsonis, N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Neely, M.
Right arrow Articles by Kartsonis, N. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2009, p. 1450-1456, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01027-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics and Safety of Caspofungin in Older Infants and Toddlers {triangledown}

Michael Neely,1 Hasan S. Jafri,2 Nita Seibel,3 Katherine Knapp,4 Peter C. Adamson,5 Susan K. Bradshaw,6 Kim M. Strohmaier,6 Peng Sun,6 Sheng Bi,6 Marissa Fallon Dockendorf,6 Julie A. Stone,6 and Nicholas A. Kartsonis6*

Children's Hospital, Los Angeles, California,1 University of Texas Southwestern Medical Center at Dallas, Dallas, Texas,2 Children's National Medical Center, Washington, DC,3 St. Jude Children's Research Hospital, Memphis, Tennessee,4 The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania,5 Merck Research Laboratories, West Point, Pennsylvania6

Received 31 July 2008/ Returned for modification 20 November 2008/ Accepted 17 December 2008

Although information about the efficacy and safety experience with caspofungin at 50 mg/m2 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/m2 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 (AUC0-24) was 130.3 µg-h/ml, the peak concentration (C1) was 17.2 µg/ml, and the trough concentration (C24) was 1.6 µg/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 t1/2 in infants/toddlers (8.8 h) was reduced ~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/m2 daily was well tolerated in infants and toddlers; the AUC and caspofungin C24 were generally comparable to those in adults receiving caspofungin at 50 mg daily.

* Corresponding author. Mailing address: Merck Research Laboratories, P.O. Box 1000, UG3D-56, North Wales, PA 19454-1099. Phone: (267) 305-7269. Fax: (267) 305-6530. E-mail: nicholas_kartsonis{at}merck.com

{triangledown} Published ahead of print on 29 December 2008.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1450-1456, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01027-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»