title: Pharmacokinetic evaluation of liposomal amphotericin B (L-AMB) in patients with invasive fungal infection: Population approach in Japanese pediatrics.
abstract: The pharmacokinetic characteristics of liposomal amphotericin B (L-AMB; AmBisome(®)) in patients with invasive fungal infection were investigated. A population pharmacokinetic (PK) model in Japanese pediatric patients was developed based on 159 serum amphotericin B (AMPH-B) concentrations obtained in a post-marketing clinical study. The subjects were 39 patients with a mean age of 8.4 years (SD 4.5) and mean body weight of 27.1 kg (SD 14.1). A two-compartment PK model with zero-order input and first-order elimination was fitted to serum AMPH-B concentrations for L-AMB doses of 1.0, 2.5, and 5.0 mg/kg/day. Body weight showed significant correlations with PK parameters, such as clearance (CL) and distribution volume of the central compartment (Vc). The predicted Cmax/dose and AUC0-24/dose in Japanese pediatric patients were similar to those in non-Japanese pediatric patients and Japanese adult patients. Extremely large increases in Ctrough compared with predicted values were observed in some Japanese pediatric patients, but no relationships with demographic characteristics, clinical laboratory test values, or representative adverse drug reaction (decreased potassium) were found. The population PK parameters in this study are useful for simulating PK profiles of L-AMB and will be helpful for PK exposure comparisons among different populations and in investigations of pharmacokinetic-pharmacodynamic characteristics in patients.
  Amphotericin B Deoxycholate (PubChem CID:23668620); amphotericin B (PubChem CID:5280965); 3-nitrophenol (PubChem CID:11137); methanol (PubChem CID:887).
authors.affiliation: Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: yuka-ohata@ah.ds-pharma.co.jp.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ohata
authors.affiliation: Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: yoshiko-tomita@ds-pharma.co.jp.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd, 13-1 Kyobashi 1-chome, Chuo-ku, Tokyo 104-8536, Japan. Electronic address: kota-suzuki@ds-pharma.co.jp.
authors.forename: Kota
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Drug Development Division, Sumitomo Dainippon Pharma Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: takashi-maniwa@ds-pharma.co.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maniwa
authors.affiliation: Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, 5-Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address: yano@mb.kyoto-phu.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: sunakawa@med.kitasato-u.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sunakawa
mesh_terms: D000293:Adolescent; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015233:Models, Statistical; D009181:Mycoses / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000382:microbiology; D011188:Potassium / Q000097:blood; D011358:Product Surveillance, Postmarketing
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; C068538:liposomal amphotericin B; D000666:Amphotericin B; D011188:Potassium
keywords: Adverse drug reaction; Clinical laboratory test values; Invasive fungal infection; Liposomal amphotericin B; PK exposures; Pediatric patients; Population pharmacokinetics