JAC Advance Access originally published online on February 13, 2009
Journal of Antimicrobial Chemotherapy 2009 63(4):767-770; doi:10.1093/jac/dkp026
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Original research |
Pharmacokinetics of caspofungin and voriconazole in critically ill patients during extracorporeal membrane oxygenation
1 Department of Pharmacy, University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium 2 Laboratory for Pharmacotechnology and Biopharmacy, Department of Pharmaceutical Sciences, Herestraat 49, 3000 Leuven, Belgium 3 Medical Intensive Care Unit, University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium 4 Centre for Clinical Pharmacology, University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium
Received 12 August 2008; returned 6 October 2008; revised 19 January 2009; accepted 19 January 2009
* Corresponding author. Tel: +32-16-347560; Fax: +32-16-343085; E-mail: isabel.spriet{at}uz.kuleuven.be
Objectives: During extracorporeal membrane oxygenation (ECMO), drug disposition changes significantly. Plasma concentrations are altered due to an expanded circulating volume leading to a decreased elimination. In addition, adsorption and sequestration of drugs by the ECMO circuit components may further alter pharmacokinetics. Treating patients during the ECMO period with antifungals is difficult. Loss in the ECMO circuit can potentially result in sub-therapeutic levels.
Methods: Two cases are presented in which caspofungin and voriconazole levels and pharmacokinetic parameters were determined during the ECMO period.
Results: Mean caspofungin trough and peak levels were 3.73 and 11.95 µg/mL. These are comparable to previously reported ones. Also pharmacokinetic parameters were identical to those reported in the literature. It seems that caspofungin is not sequestrated by the ECMO circuit, which is expected based on its low log P value. During the first days of ECMO therapy, voriconazole trough and peak levels did not differ much from those determined prior to ECMO therapy. However, at the start of ECMO therapy, the voriconazole dose was increased from 280 to 400 mg twice daily as loss due to binding to the circuit was expected. This increase was not immediately reflected in higher voriconazole levels, which may be due to drug sequestration by the circuit. However, the voriconazole half-life was extended up to 20 h in our patient. Two days after the dose increase, levels reached troughs >10 µg/mL and peaks of around 15 µg/mL, exceeding the therapeutic interval for voriconazole. This can possibly be explained by the saturation of binding sites on the ECMO circuit.
Conclusions: Our results suggest that adequate caspofungin plasma levels are maintained during ECMO. In the case of voriconazole, it is recommended to monitor plasma levels to ensure efficacy and avoid toxicity.
Keywords: plasma levels , therapeutic drug monitoring , antifungals