TY - JOUR
T1 - Pharmacokinetics, efficacy, and safety of caspofungin in Japanese pediatric patients with invasive candidiasis and invasive aspergillosis
AU - Mori, Masaaki
AU - Imaizumi, Masue
AU - Ishiwada, Naruhiko
AU - Kaneko, Takashi
AU - Goto, Hiroaki
AU - Kato, Koji
AU - Hara, Junichi
AU - Kosaka, Yoshiyuki
AU - Koike, Kazutoshi
AU - Kawamoto, Hiroshi
AU - Maeda, Naoko
AU - Yoshinari, Tomoko
AU - Kishino, Hiroyuki
AU - Takahashi, Kenichi
AU - Kawahara, Shizuko
AU - Kartsonis, Nicholas A.
AU - Komada, Yoshihiro
N1 - Funding Information:
We appreciate the great efforts for patient enrollment from all the investigators including Keiko Asami (Niigata Cancer Center Hospital, Niigata) and Hisato Kigasawa (Kanagawa Children's Medical Center) for this study. We appreciate the support from Wendy Comisar ( Merck Research Laboratories ) and Yuki Matsumoto (MSD K. K.) on pharmacokinetic analysis. This study was sponsored by MSD K.K., Japan .
Publisher Copyright:
© 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - The antifungal agents approved in Japan for pediatric use are limited and many unapproved drugs are actually used without clear instruction for dosage. We investigated the pharmacokinetics of caspofungin for the treatment of invasive candidiasis and invasive aspergillosis in 20 Japanese pediatric patients using a pediatric-specific dosage based on body surface area. Caspofungin was administered intravenously over 60min as 70mg/m2 on Day 1, followed by 50mg/m2 per day. Five or 4 point blood sampling were done in 15 patients on Day 4-5 to calculate AUC0-24h. The geometric means (95% confidence interval) of C24h and AUC0-24h in the pediatric patients were 3.3(2.5, 4.4)μg/mL and 175.1 (139.3, 220.1)μghr/mL, respectively, which were comparable to those in Japanese adult patients [3.2 (2.8, 3.5)μg/mL and 144.9 (131.7, 159.3)μghr/mL, respectively]. Among the 20 patients, 10 (50%) had at least 1 drug-related adverse event which was considered related to caspofungin therapy. No drug-related serious adverse event and no death occurred. The most common drug-related adverse events were events relating to hepatic function (mainly increases in ALT and AST). The overall success in efficacy was observed in 13 of 20 patients. In conclusion, once daily administration of caspofungin (70mg/m2 on Day 1, followed by 50mg/m2 [maximum daily dose not to exceed 70mg]), which is the same dosage being used in overseas, achieved sufficient drug exposure and a favorable efficacy and acceptable safety profile in Japanese pediatric patients with invasive fungal infections.
AB - The antifungal agents approved in Japan for pediatric use are limited and many unapproved drugs are actually used without clear instruction for dosage. We investigated the pharmacokinetics of caspofungin for the treatment of invasive candidiasis and invasive aspergillosis in 20 Japanese pediatric patients using a pediatric-specific dosage based on body surface area. Caspofungin was administered intravenously over 60min as 70mg/m2 on Day 1, followed by 50mg/m2 per day. Five or 4 point blood sampling were done in 15 patients on Day 4-5 to calculate AUC0-24h. The geometric means (95% confidence interval) of C24h and AUC0-24h in the pediatric patients were 3.3(2.5, 4.4)μg/mL and 175.1 (139.3, 220.1)μghr/mL, respectively, which were comparable to those in Japanese adult patients [3.2 (2.8, 3.5)μg/mL and 144.9 (131.7, 159.3)μghr/mL, respectively]. Among the 20 patients, 10 (50%) had at least 1 drug-related adverse event which was considered related to caspofungin therapy. No drug-related serious adverse event and no death occurred. The most common drug-related adverse events were events relating to hepatic function (mainly increases in ALT and AST). The overall success in efficacy was observed in 13 of 20 patients. In conclusion, once daily administration of caspofungin (70mg/m2 on Day 1, followed by 50mg/m2 [maximum daily dose not to exceed 70mg]), which is the same dosage being used in overseas, achieved sufficient drug exposure and a favorable efficacy and acceptable safety profile in Japanese pediatric patients with invasive fungal infections.
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U2 - 10.1016/j.jiac.2015.01.009
DO - 10.1016/j.jiac.2015.01.009
M3 - Article
C2 - 25701307
AN - SCOPUS:84939994473
SN - 1341-321X
VL - 21
SP - 421
EP - 426
JO - Journal of Infection and Chemotherapy
JF - Journal of Infection and Chemotherapy
IS - 6
ER -
