Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure.
We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Cook
D R
DR
Department of Anesthesiology, Presbyterian-University Hospital, Pittsburgh, PA.
Freeman
J A
JA
Lai
A A
AA
Robertson
K A
KA
Kang
Y
Y
Stiller
R L
RL
Aggarwal
S
S
Abou-Donia
M M
MM
Welch
R M
RM
D000328:Adult; D000768:Anesthesia, General; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D008107:Liver Diseases / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; C049429:doxacurium