Population Pharmacokinetics of Propofol Administered by TCI in Chinese Elderly Patients
Journal of Chinese Pharmaceutical Sciences 2005, 14(3): 154-161，-0001，（）：
Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirtytwo patients with ASA Ⅰ-Ⅱ, 65-82 years old, undergoing selective lower abdominal operation were studied. Propofol was administered by target-controlled infusion with Marsh parameter. The target plasma concentration was 3μg·mL-1. Radial arterial blood samples were collected and analyzed by reversed phase HPLC with fluorescence detection. Population pharmacokinetic modeling was performed using NONMEM. Inter-individual variability and intraindividual variability of propofol were estimated for clearances and volumes of distribution. The effects of age, body weight, lean body mass, gender, height, hemoglobin, total protein, albumin, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were investigated. The effects of coadministered opioid drugs were also studied. Results The pharmacokinetics of propofol in the Chinese elderly patients was best described by a three-compartment open model. Lean body mass was found to be a covariate for system clearance at significant level (P＜01005). The clearance decreased linearly with age as well ( P < 01005) . The apparent volume of distribution for deep peripheral compartment (V3 ) was influenced by gender. Elderly female patients showed a higher value for V3 . Conclusion The pharmacokinetics of propofol administered by TCI in Chinese elderly patients can be well described by a threecompartment open model . Inclusion of age , lean body mass and gender as covariates significantly improved the model . To ensure the accuracy and precision of target2controlled infusion , the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.