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

Purpose: Dexmedetomidine (DEX) is a highly selective α-adrenoceptor agonist with high protein binding of 94%. Critical illness may affect protein binding and the pharmacokinetic (PK) parameters of many drugs, including DEX. In critically ill patients receiving prolonged infusions of DEX, there is little information documenting the relationship between key pathophysiologic factors and DEX protein binding or PK parameters.

Large inter-individual variability in pharmacokinetics of dexmedetomidine and its two major N-glucuronides in adult intensive care unit patients.

Dexmedetomidine (DMTD), an α-adrenoceptor agonist, is commonly used for sedation and analgesia in intensive care unit (ICU) patients. The primary plasma metabolites of DMTD are its direct N-glucuronides, namely N-glucuronide of dexmedetomidine (DG1) and N-glucuronide of dexmedetomidine (DG2), accounting for 41% of DMTD metabolism in healthy volunteers. Since variations on the extent of N-glucuronidation could be one of the key factors contributing to the high interpatient differences of DMTD pharmacokinetics in ICU patients and its subsequent sedative effect.

Altered Pharmacokinetics in Prolonged Infusions of Sedatives and Analgesics Among Adult Critically Ill Patients: A Systematic Review.

Purpose: The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness. The critically ill population presents challenges when titrating infusions of sedatives and analgesics to maintain optimal sedation and pain levels. This systematic review examined the PK data in critically ill adult patients with prolonged infusions (>24 hours) of commonly used sedatives and analgesics to highlight possible altered PK parameters compared with noncritically ill patients.

Prolonged infusion of sedatives and analgesics in adult intensive care patients: A systematic review of pharmacokinetic data reporting and quality of evidence.

Although pharmacokinetic (PK) data for prolonged sedative and analgesic agents in intensive care unit (ICU) has been described, the number of publications in this important area appear relatively few, and PK data presented is not comprehensive. Known pathophysiological changes in critically ill patients result in altered drug PK when compared with non-critically ill patients. ClinPK Statement was recently developed to promote consistent reporting in PK studies, however, its applicability to ICU specific PK studies is unclear.