The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment

Dexmedetomidine, an alpha (2)-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexme-detomidine have not been determined in humans with impaired renal function, we studied them in volunteers with severe renal disease and in control volunteers. Six volunteers with severe renal disease and six matched volunteers with normal renal function received dexmedetomidine, 0.6 mug/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentrations were drawn before, during, and up to 12 h after the infusion. Two-compartmental pharmacokinetic models were fit to the drug concentration versus time data. We also determined its hemodynamic, respiratory, and sedative effects. There was no difference between Renal Disease and Control groups in either volume of distribution at steady state (1.81 +/- 0.55 and 1.54 +/- 0.08 L/kg, respectively; mean +/- SD) or elimination clearance (12.5 +/- 4.6 and 8.9 +/- 0.7mL . min(-1) . kg(-1), respectively). However, elimination half-life was shortened in the Renal Disease group (113.4 +/- 11.3 vs 136.5 +/- 13.0 min; P < 0.05). A mild reduction in blood pressure occurred in most volunteers. Although most volunteers were sedated by dexmedetomidine, renal disease volunteers were sedated for a longer period of time.