Mechanistic Considerations and Pharmacokinetic Implications on Concomitant Drug Administration During CytoSorb
Joerg Scheier1, Peter J Nelson2, Antoine Schneider3,4
1CytoSorbents Europe GmbH, Berlin, Germany.
Insights
The CytoSorb hemoadsorption device can affect how drugs are processed in the body. This review offers guidance on adjusting drug doses during CytoSorb therapy, considering drug removal rates and patient factors.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Biomedical Engineering
Background:
- The CytoSorb hemoadsorption device is widely used in critical care settings.
- Its use necessitates understanding potential impacts on drug pharmacokinetics (PK).
- Managing concomitant drug administration during CytoSorb therapy requires careful consideration.
Purpose of the Study:
- To review mechanistic principles of drug removal by CytoSorb.
- To synthesize available preclinical and clinical data on drug-device interactions.
- To provide guidance for drug dosing during CytoSorb therapy.
Main Methods:
- Conducted a detailed literature search of PubMed and OVID MEDLINE databases.
- Included human, animal, and bench-top studies reporting PK or drug removal data.
- Excluded studies focused on CytoSorb for drug overdose treatment.
Main Results:
- PK data exist for over 50 drugs across various classes.
- Drugs were categorized by removal rates (low, moderate, high) or clearance increase.
- General dosing guidance was developed based on available data and clinical context.
Conclusions:
- CytoSorb therapy can alter drug elimination, with variable removal rates.
- Clinical significance depends on patient-specific factors and the extracorporeal platform.
- Guidance is provided, but clinical judgment and therapeutic drug monitoring are essential.
Abstract:
The CytoSorb hemoadsorption device (CytoSorbents Inc, Monmouth Junction, NJ) is increasingly used in many critical disease states. The potential impact on the pharmacokinetic (PK) of concomitantly administered drugs must be considered in clinical practice. The current review summarizes relevant mechanistic principles, available preclinical and clinical data, and provides general guidance for the management of concomitant drug administration during CytoSorb therapy.
Data Sources:
Detailed search strategy using the PubMed and OVID MEDLINE databases, as well as presented congress abstracts for studies on drug removal by the CytoSorb device.
Study Selection:
Human, animal, and bench-top studies with PK or drug-removal data during CytoSorb therapy were selected for inclusion. Publications reporting on CytoSorb treatments for drug overdose were not considered.
Data Extraction:
Relevant PK data were examined and synthesized for narrative review.
Data Synthesis:
To date, PK data during CytoSorb hemoadsorption are available for more than 50 drugs, including analgesics, antiarrhythmics, anticonvulsants, antidepressants, antihypertensives, antiinfectives, antithrombotics, anxiolytics, and immunosuppressants. Based on available PK data, drugs were categorized into low (<30%), moderate (30-60%), or high rates of removal (>60%), or, alternatively, according to clearance increase relative to endogenous clearance: negligible (<25%), low (25-100%), moderate (100-400%), or high (>400%). In most reports, additional impact of the extracorporeal platform where CytoSorb was integrated was not available. Based on available data and considering drug, patient, and setup-specific aspects, general dosing guidance for clinical practice was developed.
Conclusions:
CytoSorb therapy may increase drug elimination through active removal. However, the extent of removal is heterogeneous, and its clinical significance, if any, depends on the broader clinical context, including a patient's specific endogenous drug clearance and the underlying extracorporeal platform used. The available data, although not definitive, allow for general guidance on dosing adjustments during CytoSorb therapy; however, any treatment decisions should always be complemented by clinical judgment and therapeutic drug monitoring, when available.
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