TY - JOUR
T1 - The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment
AU - De Wolf, Andre M.
AU - Fragen, Robert J.
AU - Avram, Michael J.
AU - Fitzgerald, Paul C.
AU - Rahimi-Danesh, Farhad
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Dexmedetomidine, an α2-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 μg/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 · 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.
AB - Dexmedetomidine, an α2-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 μg/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 · 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.
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U2 - 10.1097/00000539-200111000-00031
DO - 10.1097/00000539-200111000-00031
M3 - Article
C2 - 11682398
AN - SCOPUS:0034761921
SN - 0003-2999
VL - 93
SP - 1205
EP - 1209
JO - Anesthesia and analgesia
JF - Anesthesia and analgesia
IS - 5
ER -