Pharmacokinetics of morphine in patients following orthotopic liver transplantation.

Plasma and urine concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide were measured in seven patients after orthotopic liver transplantation. After a single i.v. bolus of morphine sulphate 10 mg a biexponential decay was observed. Although the distribution and elimination half-lives for morphine were similar to those described in previous studies, a greater total apparent volume of distribution was observed. This was reflected in a greater plasma clearance of morphine than has been reported previously. The concentration of morphine glucuronides remained increased 24 h after administration of morphine; the clinical significance of this remains to be established. The metabolism of morphine was virtually complete, with 4.5% unchanged morphine recovered in urine 24 h after drug administration.