The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment.
Dexmedetomidine, an alpha2-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexmedetomidine 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 microg/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 +/- 0.7 mL x min(-1) x 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.


CONCLUSIONS
The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment differed little from those in volunteers with normal renal function. In addition, there were no clinically significant differences in the hemodynamic responses to dexmedetomidine. However, dexmedetomidine resulted in more prolonged sedation in subjects with renal disease.
De Wolf
A M
AM
Departments of Anesthesiology, Northwestern University Medical School, Chicago, Illinois 60611, USA. a-dewolf@nwu.edu
Fragen
R J
RJ
Avram
M J
MJ
Fitzgerald
P C
PC
Rahimi-Danesh
F
F
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D020927:Dexmedetomidine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D007674:Kidney Diseases / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D003404:Creatinine