The Pharmacokinetics of Dexmedetomidine in Volunteers with Severe Renal Impairment Andre M. De Wolf, MD*, Robert J. Fragen, MD*, Michael J. Avram, PhD*, Paul C. Fitzgerald, BSN, MS*, and Farhad Rahimi-Danesh, MD† Departments of *Anesthesiology and †Nephrology, Northwestern University Medical School, Chicago, Illinois Dexmedetomidine, an  2 -adrenergic agonist with seda- tive 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 vol- unteers with normal renal function received dexmedeto- midine, 0.6 g/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentra- tions 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 seda- tive effects. There was no difference between Renal Dis- ease and Control groups in either volume of distribution at steady state (1.81  0.55 and 1.54  0.08 L/kg, respec- tively; mean  sd) or elimination clearance (12.5  4.6 and 8.9  0.7 mL · min -1 · kg -1 , respectively). However, elim- ination half-life was shortened in the Renal Disease group (113.4  11.3 vs 136.5  13.0 min; P  0.05). A mild reduc- tion in blood pressure occurred in most volunteers. Al- though most volunteers were sedated by dexmedetomi- dine, renal disease volunteers were sedated for a longer period of time. (Anesth Analg 2001;93:1205–9) D exmedetomidine is a selective  2 -adrenergic ag- onist with sedative and analgesic properties. In addition, dexmedetomidine reduces anesthetic requirements (1,2). It causes dose-dependent decreases in blood pressure and heart rate that are associated with a decrease in plasma norepinephrine concentrations, but it is still well tolerated hemodynamically (3). In animal models, dexmedetomidine is mainly biotransformed in the liver, with limited renal elimination clearance (4,5). Dexmedetomidine pharmacokinetics in humans with impaired renal function have not been determined. This study was designed to compare the pharmacokinetics of dexmedetomidine in volunteers with severe renal im- pairment with those in healthy volunteers. In addition, sedative, hemodynamic, and respiratory effects were assessed. Methods After obtaining IRB approval and written informed consent from all subjects, six volunteers with severe renal disease (RD group) and six matched volunteers with normal renal function (C group) were entered into this study. The C group volunteers were matched by weight, age, sex, and smoking status. Within 21 days of the study, a prestudy 24-h creatinine clear- ance (Cl CR ) test needed to be 30 mL/min in the volunteers with RD and 80 mL/min in the healthy volunteers for them to be enrolled in the study. Vol- unteers with RD had stable RD and had not yet un- dergone dialysis or renal transplantation. They could also not enter the study if they had other uncontrolled systemic disease (e.g., uncontrolled systemic hyper- tension [systolic blood pressure 180 mm Hg and diastolic blood pressure 100 mm Hg]; congestive heart failure; uncontrolled diabetes; gastrointestinal, neurologic, hematologic, hepatic, or psychiatric dis- ease; significant electrolyte imbalance; or uncontrolled hypo- or hyperthyroidism). All volunteers were aged 18 – 65 yr, had a medical and social history and physical examination, had a hemoglobin concentration of 9 g/dL, and had neg- ative pregnancy, drug screening, alcohol, hepatitis B, and human immunodeficiency virus tests. Women had to be nonlactating. A 12-lead electrocardiogram Supported by a research grant from Abbott Laboratories, Abbott Park, IL, and by institutional or departmental sources. Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, FL, October 17–21, 1998. Accepted for publication June 11, 2001. Address correspondence and reprint requests to A. De Wolf, MD, Department of Anesthesiology, 251 East Huron, Passavant 360, Chicago, IL 60611. Address e-mail to a-dewolf@nwu.edu. ©2001 by the International Anesthesia Research Society 0003-2999/01 Anesth Analg 2001;93:1205–9 1205