Pharmacokinetics and Pharmacodynamics of Pipecuronium in Patients with Cirrhosis

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Abstract

To determine the effect of liver cirrhosis on the pharmacokinetics and pharmacodynamics of pipecuronium, the authors administered 100 μg/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 μg/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 ± 1.05mL·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 μg/kg).

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