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静脉-静脉体外膜肺氧合对利托那韦、达芦那韦、替诺福韦和拉米夫定药代动力学的影响。

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

作者信息

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

机构信息

The North West Heart and Lung Centre, The University Hospital of South Manchester, Manchester M23 9LT, United Kingdom.

Manchester Pharmacy School, The University of Manchester, Manchester M13 9PT, United Kingdom.

出版信息

J Crit Care. 2017 Aug;40:113-118. doi: 10.1016/j.jcrc.2017.03.010. Epub 2017 Mar 12.

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.

摘要

引言

据我们所知,目前尚无关于接受体外膜肺氧合(ECMO)治疗的患者抗逆转录病毒(ART)药物药代动力学(PK)特征的公开数据。我们报告了一名需要静脉-静脉ECMO(VV ECMO)的HIV患者中利托那韦、达芦那韦、拉米夫定和替诺福韦的PK分析。

方法

在患者接受ECMO治疗期间,在进行预先剂量调整后获取利托那韦、达芦那韦、替诺福韦和拉米夫定的血浆浓度。使用已发表的群体PK模型来模拟这些药物的血浆浓度曲线。然后,使用个体贝叶斯事后参数估计值,将群体预测值和观察到的血浆浓度与预期的药物曲线进行叠加。

结果

在剂量调整后,利托那韦、达芦那韦和替诺福韦的PK曲线落在预期范围内,并且与群体预测值相似,尽管利托那韦略有不同。拉米夫定的观察数据及其PK曲线与文献中的数据完全不同。

结论

据我们所知,这是第一项报告ECMO治疗期间ART药物PK特征的研究。根据我们的结果,在VV ECMO期间对ART药物进行剂量调整可能是可取的。需要对拉米夫定的PK特征进行进一步研究。

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