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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 10/2017

Open Access 01-10-2017 | Original Research Article

Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

Authors: Lisa C. Martial, Rob ter Heine, Jeroen A. Schouten, Nicole G. Hunfeld, Henk J. van Leeuwen, Paul E. Verweij, Dylan W. de Lange, Peter Pickkers, Roger J. Brüggemann

Published in: Clinical Pharmacokinetics | Issue 10/2017

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Abstract

Objective

To study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strategies.

Methods

Micafungin PK data from 20 intensive care unit patients were available. A population-PK model was developed. Various dosing regimens were simulated: licensed regimens (I) 100 mg daily; (II) 100 mg daily with 200 mg from day 5; and adapted regimens 200 mg on day 1 followed by (III) 100 mg daily; (IV) 150 mg daily; and (V) 200 mg daily. Target attainment based on a clinical PK target for Candida as well as non-Candida parapsilosis infections was assessed for relevant minimum inhibitory concentrations [MICs] (Clinical and Laboratory Standards Institute). Parameter uncertainty was taken into account in simulations.

Results

A two-compartment model best fitted the data. Clearance was 1.10 (root square error 8%) L/h and V 1 and V 2 were 17.6 (root square error 14%) and 3.63 (root square error 8%) L, respectively. Median area under the concentration–time curve over 24 h (interquartile range) on day 14 for regimens I–V were 91 (67–122), 183 (135–244), 91 (67–122), 137 (101–183) and 183 (135–244) mg h/L, respectively, for a typical patient of 70 kg. For the MIC/area under the concentration–time curve >3000 target (all Candida spp.), PK target attainment was >91% on day 14 (MIC 0.016 mg/L epidemiological cut-off) for all of the dosing regimens but decreased to (I) 44%, (II) 91%, (III) 44%, (IV) 78% and (V) 91% for MIC 0.032 mg/L. For the MIC/area under the concentration–time curve >5000 target (non-C. parapsilosis spp.), PK target attainment varied between 62 and 96% on day 14 for MIC 0.016.

Conclusions

The licensed micafungin maintenance dose results in adequate exposure based on our simulations with a clinical PK target for Candida infections but only 62% of patients reach the target for non-C. parapsilosis. In the case of pathogens with an attenuated micafungin MIC, patients may benefit from dose escalation to 200 mg daily. This encourages future study.
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Metadata
Title
Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients
Authors
Lisa C. Martial
Rob ter Heine
Jeroen A. Schouten
Nicole G. Hunfeld
Henk J. van Leeuwen
Paul E. Verweij
Dylan W. de Lange
Peter Pickkers
Roger J. Brüggemann
Publication date
01-10-2017
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 10/2017
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-017-0509-5

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