title: Pharmacokinetics and pharmacodynamics of pipecuronium in patients with cirrhosis.
abstract: To determine the effect of liver cirrhosis on the pharmacokinetics and pharmacodynamics of pipecuronium, the authors administered 100 micrograms/kg of pipecuronium intravenously to eight patients with liver cirrhosis and eight patients with normal liver and renal function undergoing elective abdominal surgery. All patients were anesthetized with thiopental (5-7 mg/kg), nitrous oxide (50-70% in oxygen), and fentanyl in repeated doses (2 micrograms/kg). Plasma concentrations of pipecuronium were determined by high-pressure liquid chromatography. A two-compartment open model was used for pharmacokinetic analysis. Thumb-elicited mechanical response to single-twitch ulnar nerve stimulation was also measured. Total plasma clearance did not differ between controls (2.96 +/- 1.05 mL.min-1.kg-1, mean +/- SD) and cirrhotics (2.61 +/- 1.16 mL.min-1.kg-1). Terminal elimination half-life was 111 +/- 46 min in controls and 143 +/- 25 min in cirrhotics. The total apparent volume of distribution at steady state did not differ between controls (350 +/- 81 mL/kg) and cirrhotics (452 +/- 222 mL/kg). The volume of the central compartment was not different between the two groups. The onset of neuromuscular blocking effect was longer in cirrhotics (233 +/- 112 s) (P < 0.05) than in controls (170 +/- 33 s). The clinical duration (injection until single twitch returned to 25%) was similar between the two groups: 167 +/- 41 min in controls and 165 +/- 48 min in cirrhotics. The authors conclude that hepatic insufficiency due to cirrhosis does not alter the pharmacokinetics and pharmacodynamics of pipecuronium (100 micrograms/kg).
authors.affiliation: Department of Anesthesia, Henri Mondor Hospital, University Paris-Val de Marne, Creteil, France.
authors.forename: G
authors.initials: G
authors.lastname: D'Honneur
authors.forename: M
authors.initials: M
authors.lastname: Khalil
authors.forename: C
authors.initials: C
authors.lastname: Dominique
authors.forename: J P
authors.initials: JP
authors.lastname: Haberer
authors.forename: U W
authors.initials: UW
authors.lastname: Kleef
authors.forename: P
authors.initials: P
authors.lastname: Duvaldestin
mesh_terms: D000005:Abdomen / Q000601:surgery; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D017558:Elective Surgical Procedures; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D017300:Pipecuronium / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D017300:Pipecuronium