Population pharmacokinetics of remifentanil in patients undergoing orthotopic liver transplantation.
BACKGROUND
Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation (OLT) and the influence of relevant factors.


METHODS
Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 microg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 (baseline), 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling (NONMEM).


RESULTS
The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment (V(1)) and the volume of distribution in the peripheral compartment (V(2)) were influenced by body weight.


CONCLUSIONS
The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V(1) and V(2).
Zhang
Li-ping
LP
Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
Yang
Lu
L
Bi
Shan-shan
SS
Lu
Wei
W
Zhang
Xian-hua
XH
Zhai
Suo-di
SD
Duan
Li-ping
LP
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077208:Remifentanil; D053719:Tandem Mass Spectrometry
D010880:Piperidines; D000077208:Remifentanil