The effect of veno-venous ECMO on the pharmacokinetics of Ritonavir, Darunavir, Tenofovir and Lamivudine

Mohamed A. Ghazi Suliman, Kayode Ogungbenro, Christos Kosmidis, Alan Ashworth, Julian Barker, Anita Szabo-Barnes, Andrew Davies, Lee Feddy, Igor Fedor, Tim Hayes, Sarah Stirling, Ignacio Malagon

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Abstract

Introduction

To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV-ECMO).

Methods

Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments. Published population PK models were used to simulate plasma concentration profiles for the drugs. The population prediction and the observed plasma concentrations were then overlaid with the expected drug profiles using the individual Bayesian post-hoc parameter estimates.

Results

Following dose adjustments, the PK profiles of Ritonavir, Darunavir and Tenofovir fell within the expected range and appeared similar to the population prediction, although slightly different for Ritonavir. The observed data for Lamivudine and its PK profile were completely different from the data available in the literature.

Conclusions

To our knowledge, this is the first study reporting the PK profile of ART drugs during ECMO therapy. Based on our results, dose adjustment of ART drugs while on VV-ECMO may be advisable. Further study of the PK profile of Lamivudine is required.
Original languageEnglish
Pages (from-to)113-118
JournalJournal of Critical Care
Volume40
Early online date12 Mar 2017
DOIs
Publication statusPublished - Aug 2017

Keywords

  • Extracorporeal membrane oxygenation
  • ECMO
  • veno-venous extracorporeal membrane oxygenation
  • VV ECMO
  • pharmacokinetics
  • PK
  • antiretrovirals
  • ARTs

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