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Micafungin antifungal prophylaxis in children undergoing HSCT: can we give higher doses, less frequently? A pharmacokinetic study
- Source :
- Journal of Antimicrobial Chemotherapy. 73:1651-1658
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- Background Micafungin has a distinct advantage for antifungal prophylaxis in HSCT owing to its better safety profile, specifically in terms of hepatic and renal toxicity. In children, prophylactic micafungin is given as either 1 mg/kg every day or 3 mg/kg every other day. Objectives We performed a prospective single-centre observational study that investigated the pharmacokinetics (PK) of a single 5 mg/kg dose of micafungin in young children undergoing HSCT, to ascertain the eventual feasibility of twice-weekly prophylactic administration. Methods Nine children, ≤10 years of age undergoing HSCT, were enrolled and received a single intravenous dose of 5 mg/kg micafungin. Blood samples were obtained for PK analysis. Micafungin plasma concentration of >0.2 mg/L was chosen for target attainment (i.e. considered adequate prophylactic concentration). In addition, a population PK model was developed based on current and our previous PK study data. We also evaluated PK model-based simulation of PK profiles and target attainment using Monte Carlo simulation, for several dosing scenarios. Results Mean clearance was 15.3 mL/h/kg (range 11.0-21.4 mL/h/kg) and the mean elimination half-life was 11.6 h (range 7.8-16.6 h). The mean concentration at 96 h was 0.11 mg/L (range 0.03-0.26 mg/L). Eleven percent (n = 1) of patients achieved target attainment at the end of 96 h. Simulation data showed that 1 mg/kg daily dosing and 3 mg/kg alternate-day dosing strategies achieved at least 99% and 81% target attainment, respectively, whereas a 5 mg/kg with 3 day-interval dosing strategy resulted in 64%, 72% and 84% target attainments in patients with body weights of 10, 20 and 30 kg, respectively. Conclusions Micafungin at 5 mg/kg dosing did not achieve target attainment at the end of 96 h for antifungal prophylaxis in children undergoing HSCT. Simulation data suggest that a dosing strategy of micafungin at 5 mg/kg every 72 h is more likely to achieve target attainment in children with a higher body weight in comparison with children with a lower body weight. A cautious approach is advisable when using a high, but less frequent, dosing strategy in very young children.
- Subjects :
- Male
0301 basic medicine
Microbiology (medical)
Antifungal
medicine.medical_specialty
Antifungal Agents
medicine.drug_class
medicine.medical_treatment
030106 microbiology
Population
Hematopoietic stem cell transplantation
030226 pharmacology & pharmacy
Gastroenterology
Drug Administration Schedule
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Internal medicine
medicine
Humans
Pharmacology (medical)
Prospective Studies
Dosing
Child
Prospective cohort study
education
Candida
Pharmacology
education.field_of_study
business.industry
Hematopoietic Stem Cell Transplantation
Micafungin
Infant
Drugs, Investigational
Infectious Diseases
Mycoses
Child, Preschool
Toxicity
Administration, Intravenous
Female
business
Monte Carlo Method
medicine.drug
Subjects
Details
- ISSN :
- 14602091 and 03057453
- Volume :
- 73
- Database :
- OpenAIRE
- Journal :
- Journal of Antimicrobial Chemotherapy
- Accession number :
- edsair.doi.dedup.....73bf777d92549b28c6f977edb9826783