THE PHARMACOKINETICS AND NEUROMUSCULAR EFFECTS OF ROCURONIUM BROMIDE IN PATIENTS WITH LIVER-DISEASE

To determine the effect of liver disease on the pharmacokinetics of ro curonium, the authors administered 0.6 mg/kg (twice the ED(95)) to 10 patients with liver disease and compared these results to values in 10 healthy surgical patients. Anesthesia was induced with thiopental and maintained with isoflurane (0.9%-1.1% end-tidal concentration) and ni trous oxide (60%). Venous blood samples were obtained for 6 h after ro curonium injection and plasma concentrations were measured using gas c hromatography. Pharmacokinetic differences between groups were determi ned using a population-based pharmacokinetic analysis (NONMEM). Hepati c impairment did not alter the plasma clearance of rocuronium (217 +/- 21.8 mL/min, mean +/- SE, for both groups), but did increase the volu me of the central compartment (5.96 +/- 1.01 L for controls, 7.87 +/- 1.33 L for patients with liver disease) and volume of distribution at steady state (16.4 L for controls, 23.4 L for patients with liver dise ase). In turn, elimination half-life was longer in patients with liver disease (111 min) compared to controls (75.4 min). The authors conclu de that Liver disease alters the pharmacokinetics of rocuronium by inc reasing its volume of distribution. The longer elimination half-life m ight result in a longer duration of action of rocuronium in patients w ith liver disease, particularly after prolonged administration.