title: The influence of renal failure on the pharmacokinetics and duration of action of pipecuronium bromide in patients anesthetized with halothane and nitrous oxide.
abstract: 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)
authors.affiliation: Department of Anesthesia, University of California San Francisco 94143-0648.
authors.forename: J E
authors.initials: JE
authors.lastname: Caldwell
authors.forename: P C
authors.initials: PC
authors.lastname: Canfell
authors.forename: K P
authors.initials: KP
authors.lastname: Castagnoli
authors.forename: D P
authors.initials: DP
authors.lastname: Lynam
authors.forename: M R
authors.initials: MR
authors.lastname: Fahey
authors.forename: D M
authors.initials: DM
authors.lastname: Fisher
authors.forename: R D
authors.initials: RD
authors.lastname: Miller
mesh_terms: 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
chemical_list: D000732:Androstanols; D009466:Neuromuscular Blocking Agents; D010879:Piperazines; D017300:Pipecuronium; D015113:Androstane-3,17-diol; D009609:Nitrous Oxide; D006221:Halothane