# Pharmacokinetics of Dexmedetomidine in an In Vitro Circuit Model and In Vivo Extracorporeal Membrane Oxygenation Rat Model

## TL;DR

This study investigates how extracorporeal membrane oxygenation (ECMO) affects the drug clearance of dexmedetomidine, potentially impacting its effectiveness or safety.

## Contribution

The study introduces an in vitro circuit model and an in vivo rat model to demonstrate how ECMO alters the pharmacokinetics of dexmedetomidine.

## Key findings

- DEX recovery decreased in the in vitro circuit model after injection.
- ECMO significantly reduced DEX clearance by 75% in the in vivo rat model.
- ECMO may increase the risk of DEX-related side effects or reduce its therapeutic effect.

## Abstract

Background and objectives: Extracorporeal membrane oxygenation (ECMO) causes variability in the pharmacokinetics (PK) of drugs. Fluctuations in the PK profile of dexmedetomidine (DEX) might significantly reduce the likelihood of obtaining a therapeutic effect. The study aimed to clarify the effect of ECMO on the PK of DEX.

Methods: In vitro circuit and in vivo rat models were developed, both of which involved a bolus injection of DEX and concentration monitoring. In the in vivo model experiment, rats that underwent ECMO were compared with a control group. PK analysis of in vivo data (noncompartmental analysis and nonlinear mixed-effects modeling) was carried out to determine the effect of ECMO.

Results: In the in vitro model experiment, the expected recovery (%) of DEX decreased after injection into the circuits. In vivo PK analysis showed that the ECMO significantly influenced the clearance of DEX, which was 75% lower in the presence of ECMO than in the absence of ECMO.

Conclusion: These results suggest that ECMO may affect the efficacy or increase the risk of side effects associated with DEX.