Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal op...Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two 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 3 μg＇ 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 intra-individual 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 aminotrans ferase （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 〈 0.005）. The clearance decreased linearly with age as well （ P 〈 0. 005）. 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 three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.展开更多
文摘Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two 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 3 μg＇ 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 intra-individual 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 aminotrans ferase （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 〈 0.005）. The clearance decreased linearly with age as well （ P 〈 0. 005）. 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 three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.
