Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care

Background. The pharmacokinetics of the alpha-2 adrenoceptor agonist dexmedetomidine were studied in 10 patients requiring postoperative sedation and mechanical ventilation in the intensive care unit (ICU), and compared with previous volunteer data. Methods. On arrival in the ICU, sedation with dexmedetomidine was commenced with a loading dose of 2.5 mug kg(-1) h(-1) over 10 min followed by a maintenance infusion of 0.7 mug kg(-1) h(-1) into a central vein. Blood samples for measurement of plasma dexmedetomidine concentrations were taken during and after sedative infusions at predetermined intervals. Pharmacokinetic variables were estimated using non-compartmental methods. In addition, non-linear mixed effects modelling was used to obtain variable estimates not readily attainable from non-compartmental methods. Respiratory and haemodynamic data were recorded to enable correlation of any adverse events with the calculated pharmacokinetic profile. Results. The harmonic mean distribution half-life of dexmedetomidine was 8.6 min and the harmonic mean terminal half-life was 3.14 h. Steady-state volume of distribution averaged 173 litres, clearance averaged 48.3 litres h(-1), and the mean residence time averaged 3.86 h. Conclusions. Mean dexmedetomidine pharmacokinetic variables seen in postoperative, intensive care patients were similar to those previously found in volunteers, with the exception of the steady-state volume of distribution. A small loading dose provided effective sedation with no adverse events.