Pharmacokinetics and pharmacodynamics of vecuronium in patients with cholestasis.

The pharmacokinetics and pharmacodynamics of vecuronium were studied in nine surgical patients with cholestasis, and in 14 patients without hepatic or renal disease. After the administration of vecuronium 0.2 mg kg-1 the plasma concentration of vecuronium and the degree of neuromuscular blockade were measured. The plasma clearance of vecuronium was decreased significantly (P less than 0.01) from 4.30 +/- 1.56 ml min-1 kg-1 (mean +/- SD) in normal patients to 2.36 +/- 0.80 ml min-1 kg-1 in patients with cholestasis. The elimination half-life was of 58 +/- 22 min in normal patients and was prolonged to 98 +/- 57 min (P less than 0.05) in patients with cholestasis. The total apparent volume of distribution was unchanged in patients with cholestasis. A prolonged neuromuscular blockade induced by vecuronium was observed in patients with cholestasis: the duration of effect from injection to 75% recovery of the twitch height was prolonged from 74 +/- 19 min in normal patients to 111 +/- 13 min in patients with cholestasis. The plasma concentration corresponding to 50% recovery from paralysis did not differ significantly between the two groups. Vecuronium has a prolonged effect in patients with cholestasis which is caused by a delay in its elimination.