Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study

Abstract

Objective To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. Methods The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. Results The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. Conclusion The pharmacokinetic parameters of micafungin were not significantly altered.

Effects of ex vivo Extracorporeal Membrane Oxygenation Circuits on Sequestration of Antimicrobial Agents

“…In vivo studies found that in infants on ECMO, the Vd of micafungin was 20–90% higher than that reported in infants not on ECMO ( 27 ). However, a prospective observational study carried out in 12 adult patients on ECMO found no significant changes in the pharmacokinetic parameters of micafungin ( 28 ). Infants have less blood volume than adults, so ECMO circuits might have a greater effect on the Vd of micafungin in infants.…”

Optimizing pharmacotherapy regimens in adult patients receiving extracorporeal membrane oxygenation: A narrative review for clinical pharmacists

“…While drug loss with micafungin in the ECMO circuit has been reported up to 74%, an observational study found no differences in PK parameters on Days 1 and 4 of treatment in patients on ECMO. 54,55 For treatment of severe infections, higher daily doses of micafungin (150-200 mg every 24 h) have been recommended. 56 Caspofungin is a highly lipophilic antifungal agent with high degree of ECMO circuit sequestration, but no significant PK alterations were reported between patients on ECMO support and matched controls.…”

“…Echinocandins are concentration‐dependent agents with both fungicidal and fungistatic activity. While drug loss with micafungin in the ECMO circuit has been reported up to 74%, an observational study found no differences in PK parameters on Days 1 and 4 of treatment in patients on ECMO 54,55 . For treatment of severe infections, higher daily doses of micafungin (150–200 mg every 24 h) have been recommended 56 .…”

Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation

“…Lopez-Sanchez et al reported the PK of micafungin in 12 adult patients on ECMO. The PK values on day 1 and day 4 showed no difference between the samples taken before the membrane and those taken after, including C max , C min , V d and CL [ 76 ]. Additionally, there was no significant difference with the AUC in samples taken before and after membrane, and on days 1 and 4.…”