title: Safety and pharmacokinetics of multiple-dose anidulafungin in infants and neonates.
abstract: Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5 mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration-time curve (range) was 75 (30-109) µg·h/ml and 98 (55-278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug-related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5 mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight-based dosing and in adult patients receiving 100 mg/day.
authors.affiliation: Department of Pediatrics, Duke University, Durham, North Carolina, USA. michael.cohenwolkowiez@duke.edu
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.forename: D K
authors.initials: DK
authors.lastname: Benjamin
authors.forename: L
authors.initials: L
authors.lastname: Piper
authors.forename: I M
authors.initials: IM
authors.lastname: Cheifetz
authors.forename: C
authors.initials: C
authors.lastname: Moran
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Aram
authors.forename: A D M
authors.initials: AD
authors.lastname: Kashuba
authors.forename: E
authors.initials: E
authors.lastname: Capparelli
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: W W
authors.initials: WW
authors.lastname: Hope
authors.forename: P B
authors.initials: PB
authors.lastname: Smith
mesh_terms: D000367:Age Factors; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002175:Candida / Q000187:drug effects; D058365:Candidiasis, Invasive / Q000378:metabolism / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D054714:Echinocandins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D000077612:Anidulafungin