No abstract

We have investigated the pharmacokinetics of remifentanil and its less potent metabolite, GR90291, in six adult patients undergoing orthotopic liver transplantation (OLT). A single bolus infusion of remifentanil 10 micrograms kg-1 min-1 was given at the beginning of the dissection and anhepatic phases of OLT. Remifentanil and GR90291 concentrations were measured in subsequent serial arterial and mixed venous blood samples. Mean arterial clearance of remifentanil was significantly greater (P = 0.02) in the dissection phase (79.54 ml min-1 kg-1) than in the anhepatic phase (39.57 ml min-1 kg-1). Steady state volumes of distribution were not significantly different. Clearance of remifentanil during the anhepatic phase was similar to that of healthy adult patients. Mean maximum concentration (Cpmax) of GR90291 was lower in the dissection phase than in the anhepatic phase (P = 0.026). There was no significant pulmonary metabolism of remifentanil.

1. An i.v. dose of 14C-propofol (0.53 mg/kg) was administered to three male and three female patients during the anhepatic phase of liver transplantation, which lasted 30-56 min after dosing. Arterial and venous blood samples, bile (T-tube drainage) and urine were collected at various times afterwards and submitted to h.p.l.c. and radioassay or specific fluorescence detection for the unchanged drug. 2. Extrahepatic metabolism was apparent during the anhepatic phase, since at 30 min post-dose, unchanged propofol comprised only 42-89% of the blood radioactivity. 3. Examination of the plasma radioactivity during the anhepatic phase in two subjects showed evidence of propofol glucuronide and 4-quinol sulphate, confirming extrahepatic metabolism of the drug. Quinol glucuronides were only detected in the liver reperfusion phase. 4. There was no evidence that the lungs contribute to the extrahepatic metabolism of propofol, since drug concentrations in the arterial blood were not less than in central venous samples. 5. During the first 24 h period, urine collected from five patients contained 7-74% dose, whilst the bile contained 0.1-0.9%. In three patients with normal renal function recovery in urine was 66-74% dose. Examination of urinary radioactivity in one subject showed the main component to be propofol glucuronide during the anhepatic phase.

Summary

The pharmacokinetics of oral controlled release morphine and metoclopramide were investigated in 20 patients in a double‐blind, randomly allocated study. The concurrent administration of metoclopramide and oral controlled release morphine led to a faster onset and increased level of sedation compared with the administration of oral controlled release morphine alone. Whilst the increased sedation may be advantageous in anaesthetic practice, it may be a potential problem in patients starting longer term therapy with these drugs.