The influence of renal failure on the pharmacokinetics and duration of action of pipecuronium bromide in patients anesthetized with halothane and nitrous oxide.
The authors determined the pharmacokinetics and duration of action of a bolus dose of pipecuronium bromide (0.07 mg.kg-1) in 40 patients anesthetized with halothane and nitrous oxide. Twenty were patients with normal renal function, undergoing a variety of surgical procedures, and 20 were undergoing cadaver renal transplantation because of end-stage renal disease. Plasma concentrations of pipecuronium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by nonlinear regression and fit to a two-compartment or three-compartment model; in addition, the data were analyzed by a non-compartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the mechanical evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The pharmacokinetic parameters derived by compartmental modelling were (normal vs. renal failure, respectively): volume of distribution at steady state (309 +/- 103 vs. 442 +/- 158 ml.kg-1, mean +/- SD), plasma clearance, (2.4 +/- 0.6 vs. 1.6 +/- 0.6 ml.kg-1.min-1), mean residence time (140 +/- 63 vs. 329 +/- 198 min), and elimination half-life (137 +/- 68 vs. 263 +/- 168 min). The same parameters as derived by the non-compartmental method were (normal vs. renal failure, respectively): volume of distribution at steady state (307 +/- 80 vs. 426 +/- 119 ml.kg-1, mean +/- SD), plasma clearance (2.4 +/- 0.6 vs. 1.6 +/- 0.6 ml.kg-1.min-1), mean residence time (134 +/- 41 vs. 323 +/- 228 min), and elimination half-life (118 +/- 35 vs. 247 +/- 168 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Caldwell
J E
JE
Department of Anesthesia, University of California San Francisco 94143-0648.
Canfell
P C
PC
Castagnoli
K P
KP
Lynam
D P
DP
Fahey
M R
MR
Fisher
D M
DM
Miller
R D
RD
D000328:Adult; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D000732:Androstanols / Q000493:pharmacokinetics*; D000769:Anesthesia, Inhalation; D002849:Chromatography, Gas; D006221:Halothane; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008875:Middle Aged; D009466:Neuromuscular Blocking Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D009609:Nitrous Oxide; D017300:Pipecuronium; D010879:Piperazines / Q000493:pharmacokinetics* / Q000494:pharmacology; D013997:Time Factors
D000732:Androstanols; D009466:Neuromuscular Blocking Agents; D010879:Piperazines; D017300:Pipecuronium; D015113:Androstane-3,17-diol; D009609:Nitrous Oxide; D006221:Halothane