The Pharmacokinetics of Midazolam Following Orthotopic Liver Transplantation

Seven patients with chronic liver disease received a 10 mg intravenous bolus dose of midazolam immediately following orthotopic liver transplantation. Plasma samples were analysed for midazolam and alpha-hydroxymidazolam by gas chromatography with electron capture detection. Data from three patients could not be evaluated. In the remaining four patients the pharmacokinetics of midazolam were essentially normal but the plasma concentrations of alpha-hydroxy-midazolam were higher than those found in healthy subjects. All patients required further sedation between 0.5 and 5 h later indicating that the duration of action of midazolam was not prolonged. These results suggest that following liver transplantation, patients have considerable drug metabolising capacity either in the liver or at extrahepatic sites.