Propofol metabolism in man during the anhepatic and reperfusion phases of liver transplantation.
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.
Gray
P A
PA
Department of Anaesthesia, Addenbrooke's Hospital, Cambridge, UK.
Park
G R
GR
Cockshott
I D
ID
Douglas
E J
EJ
Shuker
B
B
Simons
P J
PJ
D000328:Adult; D001646:Bile / Q000378:metabolism; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015424:Reperfusion; D013431:Sulfates / Q000378:metabolism
D005965:Glucuronates; D013431:Sulfates; D015742:Propofol