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

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

doi:10.1016/j.jcrc.2017.03.010

Cited by 7 publications

(7 citation statements)

References 17 publications

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“…Based on the results from the study by Ghazi Suliman et al ( 23 ), the concentrations were observed in an expected range based on the model prediction while darunavir concentrations showed higher than the expected values for a typical individual with the regimen of 800 mg every 12 hours during the ECMO therapy. They suggested that the aggressive darunavir/ritonavir regimen of 800/100 mg every 12 hours as an antiretroviral therapy was appropriate in patients requiring the ECMO ( 23 ). We recommend not adjusting the darunavir/ritonavir dosing regimens as recommended for the COVID-19 but may increase the dose up to 800/100 mg every 12 hours as needed.…”

Section: Patients Receiving Ecmomentioning

confidence: 93%

“…Darunavir (high logP, PB) has high possibility of drug lost in the circuit, whereas ritonavir has the moderate to high probability to be sequestrated due to the high PB and moderate logP. Based on the results from the study by Ghazi Suliman et al ( 23 ), the concentrations were observed in an expected range based on the model prediction while darunavir concentrations showed higher than the expected values for a typical individual with the regimen of 800 mg every 12 hours during the ECMO therapy. They suggested that the aggressive darunavir/ritonavir regimen of 800/100 mg every 12 hours as an antiretroviral therapy was appropriate in patients requiring the ECMO ( 23 ).…”

Section: Patients Receiving Ecmomentioning

confidence: 99%

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Antiviral Dosing Modification for Coronavirus Disease 2019–Infected Patients Receiving Extracorporeal Therapy

Chaijamorn

Rungkitwattanakul

Nuchtavorn

et al. 2020

Critical Care Explorations

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Previous literature regarding coronavirus disease 2019 outlined a presence of organ dysfunction including acute respiratory distress syndrome and acute kidney injury that are linked to mortality. Several patients require extracorporeal therapy. This review aims to gather available published resources including physicochemical and pharmacokinetic properties and suggests antiviral drug dosing adaptation for coronavirus disease 2019–infected critically ill patients receiving extracorporeal therapy. A literature search was performed using PubMed, clinical trial registries, and bibliographic review of textbooks and review articles. Unfortunately, no standard of pharmacologic management and recommendations of drug dosing for coronavirus disease 2019 infection for critically ill patients receiving extracorporeal therapy exist due to the limited data on pharmacokinetic and clinical studies. All available extracted data were analyzed to suggest the appropriate drug dosing adjustment. Antiviral drug dosing adjustments for critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy are presented in this review. Considering pathophysiologic changes, drug properties, and extracorporeal modalities, applying our suggestions is recommended.

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Section: Patients Receiving Ecmomentioning

confidence: 93%

Section: Patients Receiving Ecmomentioning

confidence: 99%

Antiviral Dosing Modification for Coronavirus Disease 2019–Infected Patients Receiving Extracorporeal Therapy

Chaijamorn

Rungkitwattanakul

Nuchtavorn

et al. 2020

Critical Care Explorations

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show abstract

“…A significant impact of hemodialysis on the pharmacokinetics of HCQ ( Tett et al, 1989 ) and LPV ( Gupta et al, 2008 ) is unlikely but requires confirmation since steady-state conditions are not achieved in COVID-19 patients. An impact of ECMO on chloroquine pharmacokinetics has been described ( Bagate et al, 2017 ) but no convincing data exist yet for LPV ( Ghazi Suliman et al, 2017 ). However, a significant impact of ECMO should be considered since several studies have shown altered PK profiles in this situation ( Ha and Sieg, 2017 ).…”

Section: Collection Of Covariates Affecting Dose-exposure Relationshimentioning

confidence: 99%

Concerns about pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) studies in the new therapeutic area of COVID-19 infection

et al. 2020

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In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen for this new indication of COVID-19 infection. However, available pharmacokinetic and pharmacokinetic-pharmacodynamic studies suffer from severe limitations leading to unreliable conclusions, especially in term of dosing optimization. In this paper we propose to highlight these limitations and to identify some of the major requirements that need to be addressed in designing PK and PK-PD studies in this era of COVID. A special attention should be paid to pre-analytical and analytical requirements and to the proper collection of covariates affecting dose-exposure relationships (co-medications, use of specific organ support techniques and other clinical and para-clinical data). We also promote the development of population PK and PK-PD models specifically dedicated to COVID-19 patients since those previously developed for other diseases (SEL, malaria, HIV) and clinical situations (steady-state, non-ICU patients) are not representative of severe patients. Therefore, implementation of well-designed PK and PD studies targeted to COVID-19 patients is urgently needed. For that purpose we call for multi-institutional collaborative work and involvement of clinical pharmacologists in multidisciplinary research consortia.

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“…The result exhibited that the drug levels of ritonavir were lower than the expected concentrations for a typical individual in the population, suggesting that the PK of ritonavir changed during ECMO. 79 We suggest that COVID-19 patients with ECMO may need to increase the dose regimen of lopinavir/ritonavir and conduct therapeutic drug monitoring to achieve personalized treatment. Considering IFN-α is used as topical administration, we conferred that dosing adjustment is not required during ECMO.…”

Section: Antiviral Agents In Covid-19 Patients Receiving Ecmomentioning

confidence: 99%

<p>Antiviral Agent Therapy Optimization in Special Populations of COVID-19 Patients</p>

Li¹,

Wang²,

Wang³

et al. 2020

DDDT

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global outbreak of disease. The antiviral treatment acts as one of the most important means of SARS-CoV-2 infection. Alteration of physiological characteristics in special populations may lead to the change in drug pharmacokinetics, which may result in treatment failure or increased adverse drug reactions. Some potential drugs have shown antiviral effects on SARS-CoV-2 infections, such as chloroquine, hydroxychloroquine, favipiravir, lopinavir/ritonavir, arbidol, interferon alpha, and remedsivir. Here, we reviewed the literature on clinical effects in COVID-19 patients of these antiviral agents and provided the potential antiviral agent options for pregnant women, elderly patients, liver or renal dysfunction patients, and severe or critically ill patients receiving renal replacement therapy or ECMO after SARS-CoV-2 infection.

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

Abstract: 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.

Cited by 7 publications

References 17 publications

Antiviral Dosing Modification for Coronavirus Disease 2019–Infected Patients Receiving Extracorporeal Therapy

Antiviral Dosing Modification for Coronavirus Disease 2019–Infected Patients Receiving Extracorporeal Therapy

Concerns about pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) studies in the new therapeutic area of COVID-19 infection

<p>Antiviral Agent Therapy Optimization in Special Populations of COVID-19 Patients</p>

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