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.