PHARMACOKINETICS AND PHARMACODYNAMICS OF VERCURONUIUM IN PATIENTS WITH CHOLESTASIS

pharmacokinetics and pharmacodynamics of vecuronium were studiedin nine surgical patients with cholestasis, and in 14 patientswithout hepatic or renal disease. After the administration ofvecuronium 0.2 mg kg^–1 the plasma concentration of vecuroniumand the degree of neuromuscular blockade were measured. Theplasma clearance of vecuronium was decreased significantly (P< 0.01) from 4.30± 1.56 ml min^–1 kg^–1(mean±SD) in normal patients to 2.36± 0.80 mlmin^–1 kg^–1 in patients with cholestasis. The eliminationhalf-life was of 58±22 min in normal patients and wasprolonged to 98±57 min (P < 0.05) in patients withcholestasis. The total apparent volume of distribution was unchangedin patients with cholestasis. A prolonged neuromuscular blockadeinduced by vecuronium was observed in patients with cholestasis:the duration of effect from injection to 75% recovery of thetwitch height was prolonged from 74 ± 19 min in normalpatients to 111 ± 13 min in patients with cholestasis.The plasma concentration corresponding to 50% recovery fromparalysis did not differ significantly between the two groups.Vecuronium has a prolonged effect in patients with cholestasiswhich is caused by a delay in its elimination.