title: Pharmacokinetics, efficacy, and safety of caspofungin in Japanese pediatric patients with invasive candidiasis and invasive aspergillosis.
abstract: 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 60 min as 70 mg/m(2) on Day 1, followed by 50 mg/m(2) per day. Five or 4 point blood sampling were done in 15 patients on Day 4-5 to calculate AUC0-24 h. The geometric means (95% confidence interval) of C24 h and AUC0-24 h in the pediatric patients were 3.3(2.5, 4.4) μg/mL and 175.1 (139.3, 220.1) μg hr/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) μg hr/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 (70 mg/m(2) on Day 1, followed by 50 mg/m(2) [maximum daily dose not to exceed 70 mg]), 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.
authors.affiliation: Department of Pediatrics, Yokohama City University Medical Center, Urafune 4-57, Minami-ku, Yokohama, Kanagawa, Japan. Electronic address: mmori@med.yokohama-cu.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Miyagi Children's Hospital, Miyagi, Japan.
authors.forename: Masue
authors.initials: M
authors.lastname: Imaizumi
authors.affiliation: Chiba University Hospital, Chiba, Japan.
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Ishiwada
authors.affiliation: Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Kanagawa Children's Medical Center, Kanagawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Goto
authors.affiliation: Japanese Red Cross Nagoya Daiichi Hospital, Aichi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Osaka City General Hospital, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.affiliation: Hyogo Prefectural Kobe Children's Hospital, Hyogo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Ibaraki Children's Hospital, Ibaraki, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Koike
authors.affiliation: National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.affiliation: National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshinari
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishino
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Japan Development, MSD K.K., Tokyo, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kawahara
authors.affiliation: Merck Research Laboratories, Merck Sharp & Dohme Corp., Upper Gwynedd, PA, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kartsonis
authors.affiliation: Mie University Hospital, Mie, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D001228:Aspergillosis / Q000188:drug therapy*; D058365:Candidiasis, Invasive / Q000188:drug therapy*; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions; D054714:Echinocandins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D055666:Lipopeptides; D008297:Male; D011446:Prospective Studies
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin
keywords: Caspofungin; Invasive aspergillosis; Invasive candidiasis; Japanese pediatrics; Pharmacokinetics