Pharmacokinetics of propofol and extrahepatic UGT1A6 gene expression in anhepatic rats.
OBJECTIVE
The metabolic enzyme of UDP-glucuronosyltransferase 1A6 (UGT1A6) has been considered to metabolize propofol intra- or extrahepatically. The aim of the present study was to investigate the pharmacokinetics of propofol and UGT1A6 mRNA expression in extrahepatic organs before and during the anhepatic status in rats.


METHODS
Male Sprague-Dawley rats were injected with propofol (10 mg/kg) intravenously and a blood sample was taken at 2-60 min after injection. The hepatic hilum was occluded under laparotomy and then the propofol injection and blood sampling were repeated as above 24 h later. The plasma concentrations of propofol were analyzed and UGT1A6 mRNA expression in the kidney, small intestine, lung and brain from other cohort rats at 30 and 60 min of anhepatic status were semiqualified by RT-PCR.


RESULTS
T(1/2)(alpha), T(1/2)(beta) and V(d) of propofol were not changed significantly before and during the anhepatic status. The area under curve, derived from a time-dependent concentration response curve, was significantly increased whereas plasma clearance rate was decreased significantly in the anhepatic period when compared to that in the control period, respectively. UGT1A6 mRNA expression in extrahepatic organs was significantly increased at 30 or 60 min of the anhepatic status when compared to those in the control status.


CONCLUSIONS
The pharmacokinetics of propofol during the prehepatic and anhepatic status are largely similar, which is associated with the upregulation of extrahepatic UGT1A6 gene. The marginal accumulation of propofol during anhepatic period is likely to be due to both the limited function of this metabolic pathway and physiological disturbance induced by hepatic hilum occlusion.
Gu
Jianteng
J
Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Lu
Kaizhi
K
Xia
Peiyuan
P
Tang
Min
M
Dai
Qing
Q
Ma
Daqing
D
Tao
Guocai
G
D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006498:Hepatectomy; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D015742:Propofol / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D012333:RNA, Messenger; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7; D015742:Propofol