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Published on: August 28, 2021
Pharmacokinetics of Dexmedetomidine in an In Vitro Circuit Model and In Vivo Extracorporeal Membrane Oxygenation Rat
Yuhki Sato1, Erina Mothoishi1, Rina Kakuba1
1Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, JPN.
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.
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