Population Pharmacokinetics of Teicoplanin, Levofloxacin, Piperacillin/Tazobactam, Meropenem, Vancomycin, Remifentanil, Cefepime, Cefpirome, Sufentanil, Midazolam, Clopidogrel, Ticagrelor, Prasugrel During Veno-arterial Extracorporeal Membrane Oxygenation (VA ECMO)

Study Overview
=================
Brief Summary
-----------------
Extracorporeal membrane oxygenation (ECMO) is the device which increases the supply of oxygen to the body tissues in vitro and to assist in heart and lung function. Venoarterial (VA) ECMO is used in patients with cardiogenic shock, cardiac arrest, ventricular arrhythmia and is able to secure a time to self-recovery by reducing the excessive stimulation applied to the heart. However, in ECMO patients, pharmacokinetics of drugs are changing such as increased volume of distribution (Vd) or decreased clearance (CL). For this reason, it is hard to provide the best treatment in ECMO patients. The study is to evaluate whether the PK of drugs is influenced by VA ECMO and to recommend the optimal dosing strategies for proposed drugs in adult patients receiving VA ECMO.

Official Title
-----------------
Population Pharmacokinetics of Teicoplanin, Levofloxacin, Piperacillin/Tazobactam, Meropenem, Vancomycin, Remifentanil, Cefepime, Cefpirome, Sufentanil, Midazolam, Clopidogrel, Ticagrelor, Prasugrel During Veno-arterial Extracorporeal Membrane Oxygenation (VA ECMO)

Conditions
-----------------
Cardiac Dysfunction

Intervention / Treatment
-----------------
* Other: Residual blood


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patient who are ≥ 19 years old and receiving VA ECMO in Severance Hospital, Yonsei University Health System. patient who are receiving one of these drugs: teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel patients who are agreed to participate in this study Exclusion Criteria: patients who are pregnant patients who are receiving drugs that could affect study drug's concentration due to drug-drug interaction.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| On ECMO<br>patients who are concomitantly receiving teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel during ECMO | Other: Residual blood<br>* Residual blood samples(1 2 cc) at each sampling time are collected from all subjects while using ECMO for drug concentration assays(LC-MS/MS etc.).<br>|
| Off ECMO<br>patients who are concomitantly receiving teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel after removing ECMO | Other: Residual blood<br>* Residual blood samples(1 2 cc) at each sampling time are collected from all subjects while using ECMO for drug concentration assays(LC-MS/MS etc.).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum or plasma concentration | Serum or plasma concentration of teicoplanin or levofloxacin or piperacillin/tazobactam or meropenem or vancomycin or remifentanil or cefepime or cefpirome or sufentanil or midazolam or clopidogrel or ticagrelor or prasugrel | Between day0 to day3 after removing ECMO | 
| Pharmacokinetic parameter: Cmax |  | Between day0 to day3 after removing ECMO | 
| Pharmacokinetic parameter: Tmax |  | Between day0 to day3 after removing ECMO | 
| Clearance |  | Between day0 to day3 after removing ECMO | 
| volume of distribution |  | Between day0 to day3 after removing ECMO | 
| absorption rate constant | absorption rate constant (if the drug is orally administered), | Between day0 to day3 after removing ECMO | 
| elimination half life |  | Between day0 to day3 after removing ECMO | 
| area under the curve (AUC) | area under the curve (AUC) (if possible) | Between day0 to day3 after removing ECMO |