title: Pharmacokinetics and disposition of pipecuronium bromide in dogs with and without ligated renal pedicles.
abstract: The pharmacokinetics of pipecuronium bromide have been studied in anesthetized beagle dogs with and without ligated renal pedicles. A gas chromatographic assay was used to measure the plasma, urine, bile concentrations, and liver content of pipecuronium, the later of which was obtained 8 h after injection. Following an iv bolus injection of 0.1 mg/kg, pipecuronium disappeared from the plasma exponentially with distribution half-lives of 3.9 +/- 1.1 min and 12.7 +/- 9.5 min (mean +/- SD), and elimination half-lives of 44.8 +/- 2.6 min and 196.7 +/- 102.0 min in animals with and without renal pedicle ligation, respectively. Except for the volume of central compartment, all other pharmacokinetic variables differed significantly between the two experimental groups. The elimination half-life was longer (196.7 +/- 102 (SD) vs. 44.8 +/- 2.6 min), plasma clearance slower (5.9 +/- 0.8 ml.kg-1.min-1 vs. 0.9 +/- 0.1 ml.kg-1.min-1) and mean residence time longer (221 +/- 73 vs. 51.1 +/- 1.8 min) in dogs with ligated renal pedicles. Eight hours after injection, the recovery of the parent form of pipecuronium approximated 77% of the administered dose in the urine, 4.5% in the bile, and 3.3% in the liver of normal animals. In animals with ligated renal pedicles 16% of the unchanged pipecuronium was excreted into the bile and 10% of the administered dose was recovered from the liver. Since the total recovery of unaltered pipecuronium approximated 85% of the administered dose in the intact animals, biotransformation seems to play an insignificant role in disposition of this new neuromuscular blocking drug.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94143-0648.
authors.forename: K S
authors.initials: KS
authors.lastname: Khuenl-Brady
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: K
authors.initials: K
authors.lastname: Chung
authors.forename: R D
authors.initials: RD
authors.lastname: Miller
authors.forename: S
authors.initials: S
authors.lastname: Agoston
authors.forename: J E
authors.initials: JE
authors.lastname: Caldwell
mesh_terms: D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000732:Androstanols / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000378:metabolism; D004285:Dogs; D005260:Female; D006207:Half-Life; D007668:Kidney / Q000502:physiology*; D008026:Ligation; D008099:Liver / Q000378:metabolism; D009466:Neuromuscular Blocking Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017300:Pipecuronium; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000732:Androstanols; D009466:Neuromuscular Blocking Agents; D010879:Piperazines; D017300:Pipecuronium; D015113:Androstane-3,17-diol