A systematic review of dexmedetomidine pharmacology in pediatric patients

Dexmedetomidine is a centrally acting alpha-2 agonist used for initiation and maintenance of procedural sedation and mechanical ventilation in adult and pediatric settings. It is commonly used in both pediatric and neonatal intensive care units. Dexmedetomidine requires extensive titration, and patients can be over or under-sedated during titration, leading to adverse events such as hypotension and bradycardia, or inadequate sedation, which can result in self-extubation. There is a critical need to identify factors that contribute to variation in metabolism, clearance, and downstream targets of dexmedetomidine so that individualized pediatric dosing regimens can be developed. This review is focused on dexmedetomidine pharmacokinetics and pharmacodynamics in the pediatric population and dexmedetomidine-related pharmacogenes in both adults and children. We found that the strongest predictors of dexmedetomidine pharmacokinetics were age and size. Multiple pharmacogenes of significance have been identified, including ADRA2A, UGT2B10, UGT1A4, CYP1A2, CYP2A6, and CYP2D6. Evidence is weak for the correlation of these individual polymorphic genes with dexmedetomidine pharmacokinetics/dynamics, though there may be a polygenetic influence on pharmacologic response. This review provides a comprehensive overview of the genomic data gathered to date. We aim to summarize current pharmacologic studies regarding dexmedetomidine use and pharmacology in pediatric patients.