title: The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease.
abstract: To determine the effect of liver disease on the pharmacokinetics of rocuronium, the authors administered 0.6 mg/kg (twice the ED95) 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 nitrous oxide (60%). Venous blood samples were obtained for 6 h after rocuronium injection and plasma concentrations were measured using gas chromatography. Pharmacokinetic differences between groups were determined using a population-based pharmacokinetic analysis (NONMEM). Hepatic impairment did not alter the plasma clearance of rocuronium (217 +/- 21.8 mL/min, mean +/- SE, for both groups), but did increase the volume 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 disease). In turn, elimination half-life was longer in patients with liver disease (111 min) compared to controls (75.4 min). The authors conclude that liver disease alters the pharmacokinetics of rocuronium by increasing its volume of distribution. The longer elimination half-life might result in a longer duration of action of rocuronium in patients with liver disease, particularly after prolonged administration.
authors.affiliation: Department of Anesthesia, University of California, San Francisco 94115.
authors.forename: T
authors.initials: T
authors.lastname: Magorian
authors.forename: P
authors.initials: P
authors.lastname: Wood
authors.forename: J
authors.initials: J
authors.lastname: Caldwell
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: V
authors.initials: V
authors.lastname: Segredo
authors.forename: J
authors.initials: J
authors.lastname: Szenohradszky
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: L
authors.initials: L
authors.lastname: Gruenke
authors.forename: R
authors.initials: R
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000732:Androstanols / Q000493:pharmacokinetics / Q000494:pharmacology*; D000758:Anesthesia; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077123:Rocuronium
chemical_list: D000732:Androstanols; D009467:Neuromuscular Depolarizing Agents; D000077123:Rocuronium