Population pharmacokinetics of propofol in Chinese patients.
OBJECTIVE
To analyze population pharmacokinetics of propofol in Chinese surgical patients using a nonlinear mixed-effect model (NONMEM) program and to quantitate the effects of covariance of gender, age, and body weight.


METHODS
The population pharmacokinetics of propofol was investigated in 76 selective surgical patients (37 males and 39 females aged 19-77 a, weighing 39-86 kg). A total of 1439 blood samples were analyzed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Interindividual variability was estimated for clearances and distribution volumes. The effects of age, body weight, and gender were investigated.


RESULTS
The pharmacokinetics of propofol in Chinese patients was best described by a three-compartment pharmacokinetic model. Body weight was found to be a significant factor for the elimination clearance, the two inter-compartmental clearances, and the volume of the central compartment. The volumes of the shallow peripheral compartment and deep peripheral compartment remain constant for all individuals. The estimates of these parameters for a 60-kg adult were 1.56 L/min, 0.737 L/min, 0.360 L/min, 12.1 L, 43 L, and 213 L, respectively. For old patients, the elimination clearance and volume of the central compartment decreased.


CONCLUSIONS
The pharmacokinetics of propofol in Chinese patients can be well described by a standard three-compartment pharmacokinetic model. Inclusion of age and body weight as covariances significantly improved the model. Adjusting pharmacokinetics to the individual patients should improve the precision of target-controlled infusion system.
Li
Yu-Hong
YH
The School of Life Science, Nanjing University, Nanjing 210093, China. Xujguo@hotmail.com
Rui
Jian-Zhong
JZ
Zhou
Yong-Gang
YG
Wang
Li-Qin
LQ
Fu
Su-E
SE
Yang
Jian-Jun
JJ
Liu
Fu-Kun
FK
Hu
Shu-Ya
SY
Wen
Quan
Q
Xu
Jian-Guo
JG
D000328:Adult; D000367:Age Factors; D000368:Aged; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D044466:Asian People; D001835:Body Weight; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017711:Nonlinear Dynamics; D015742:Propofol / Q000493:pharmacokinetics*
D018686:Anesthetics, Intravenous; D015742:Propofol