Protein Binding and Population Pharmacokinetics of Dexmedetomidine after Prolonged Infusions in Adult Critically Ill Patients.

Dexmedetomidine (DEX) is a highly selective α Critically ill, adult intensive care unit patients at a university hospital in Hong Kong were studied. The association between the pathophysiologic changes of critical illness and protein binding was evaluated using a generalized estimating equation. A population pharmacokinetic model to establish the PK profile of DEX was developed, and key pathophysiologic covariate effects of severity of illness, organ dysfunction measures, and altered protein binding on DEX PK parameters in this critically ill population were evaluated. A total of 22 critically ill patients and 1 healthy control were included. Mean protein binding of DEX in the critically ill patients was 90.4% (95% CI, 89.1-91.7), which was 4% lower than that in the healthy control. The PK data were adequately described by a 2-compartment model. The estimated population mean (relative standard error [RSE]) values of systemic clearance (CL), volume of distribution of the central compartment (V2), intercompartmental clearance (Q), and V Although a marginally significant reduction of protein binding in critically ill patients was demonstrated, the magnitude of the difference was unlikely to be of clinical significance. Higher alanine aminotransferase concentration was associated with decreased protein binding. No significant pathophysiologic covariates were associated with the observed PK parameters. The high interindividual variability of PK parameters supports the current practice of dose titration to ensure the desired clinical effects of DEX infusion in the intensive care unit setting.

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