Am J Perinatol 2016; 33 - A001
DOI: 10.1055/s-0036-1586123

Pharmacokinetics of Micafungin Administered at High Dosages to Critically Ill Neonates and Infants with Invasive Candidiasis. Preliminary Data

C. Auriti 1, M. P. Ronchetti 1, B. M. Goffredo 2, F. Piersigilli 1, S. Cairoli 1, R. Crisafulli 1, P. Bagolan 3, A. Dotta 1
  • 1Department of Medical and Surgical Neonatology, Neonatal Intensive Care Unit, Bambino Gesù Children's Hospital, Rome, Italy
  • 2Department of Specialist Pediatrics, Biochemistry Laboratory, Bambino Gesù Children's Hospital, Rome, Italy
  • 3Department of Medical and Surgical Neonatology, Unit of Neonatal Surgery, Bambino Gesù Children's Hospital, Rome, Italy

Presenter: C. Auriti (e-mail: cinzia.auriti@opbg.net)

Introduction: It has been proposed that infants with systemic candidiasis require doses of micafungin higher than adults to reach the therapeutic effect, due to their increased plasma clearance. Concern exists on the ability of the currently recommended micafungin dosages (2–4 mg/kg/d) to achieve therapeutic targets and optimal AUCs. With this study we assessed the pharmacokinetics of higher-than-recommended dosages of micafungin administered to preterm and term neonates affected by invasive candidiasis.

Materials and Methods: 18 neonates with invasive candidiasis, 3 of them with meningitis, were treated with micafungin (Mycamine) at dosages ranging from 8 to 15 mg/kg/d i.v. plasma and cerebro spinal fluid (CSF) concentrations were measured with high performance liquid chromatography (HPLC). Systemic exposure was assessed by AUC0–24, plasma clearance (CL), and volume of distribution (Vd). Micafungin PK parameters were stratified by drug dose (10 mg/kg).

Results: AUC0–24, CL, and Vd were 282 ± 119 mg/h/L, 0.038 ± 0.017 L/h/kg, and 1.47 ± 1.16 L, respectively, without significant differences stratifying micafungin PK parameters by drug dosage. Univariate analysis showed a positive association between AUC0–24 and hepatic ALT (p = 0.018). At multivariate analysis, body weight (p < 0.001), drug dosage (p < 0.007), and AUC0–24 (p < 0.001) were significantly and independently associated with micafungin CL. In cerebrospinal fluid plasma/CSF percent ratio was 16.8± 14.1%, 3.9 ± 2.3%, 5.0 ± 2.5%, and 7.6 ± 6.7% before and at, 1, 2, and 8 hours after drug infusion. We observed no adverse events.

Conclusion: Micafungin CL increases with the dose and the body weight of infants. A significant correlation was found between micafungin AUC0–24 and hepatic transaminases. Dosages ranging between 8 and 15 mg/kg/die of micafungin enable this drug to reach therapeutic levels in CSF.

Keywords: micafungin, pharmacokinetics, candidiasis, neonates