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Study On Pharmacokenetics Of Propofol In Patients Of Different Age Groups Under General Anesthesia And Initial Evaluation On The Performance Of Target-controlled Infusion Of Propofol

Posted on:2004-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:X W XuFull Text:PDF
GTID:2144360095955663Subject:Pharmacology
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OBJECTIVE1. To establish a HPLC-ECD method for determinating propofol concentration in plasma.2. To study the pharmacokinetics of propofol in patients of different age groups under general anesthesia.3. To evaluate initially the performance of a new target-controlled infusion(TCI) system in Chinese.METHODS1. HPLC-ECD method, chromatography column, Nova-Pak Phenyl (3.9mm 150mm, 4 u m) ; Temperature, 18 -, mobile phase, methanol-phosphate buffer (pH2.8) (65: 35, v/v); flow rate, 0.9ml min-1. Electrochemical detecor was used.2. Determination of propofol concentration in plasma by HPLC-ECD. Patients were divided into 3 groups, the young group (18-44 years old) contains 11 patients (males 6 and females 5), the middle age group (45-59 years old) contains 13 patients (males 10 and females 3), the old group ( 60 years old) contains 12 patients (males 11 and female 1). After being injected single dose of propofol 2mg kg-1, the patients' venous blood samples were taken at various time to determinate the plasma concentrations of propofol by HPLC-ECD. The data were analysed by 3P87 programto get pharmacokinetics parameters, and statistics analyse by SPSS program. 3. Propofol was infusioned by a Alaris pump contained diprifusor' TC2 system. Thedata were analysed by Microsoft Excel 2000 program. RESULTS1. Determination of propofol in plasma by HPLC-ECD. Calibration curve was y = -0.00511x 0.3593 (r = 0.9999, n = 6); Linear range was covered 0.1 ~40 g -ml-1; Recovery rate of propofol was 98.0%~ 102.8% with RSD less than 2% (n = 5 ); The RSD of intra-day and inter-day assays were all less than 3% (n = 5 ); Sensitivity was 0.04pg-mL-1 (S/N 3) .2. Pharmacokinetics parameters of propofol, (1) The value of Vc, in the old group is lower than the young group (0.133 0. 052 vs 0. 326 0.073L -kg-1, P<0.01); in the middle age group is lower than the young group too (0.163 0.028 vs 0. 326 0.073 L kg-1, P <0.05); (2) The value of t1/2 , is increasing in age-depandent manner, but there are no significant difference among 3 groups (220. 18 32.12 vs 252.26 47.61 vs 284.57 29.83min, P >0.05). (3) The value of CLs, in the old group is lower than the young group (0.0184 0.0010 vs 0.0239 0.0016 L -kg-1 -min-1, P<0.05); (4) The value of AUC0- , in the old group is larger than both the middle and the young group (114.82 9.53 vs 91.02 6.35 vs 89. 67 6.58 g mL-1 min , P<0.05); and the value of AUC0-540, in the old group is large than both the middle and the young group too (103.00 9.31 vs 76.12 5.48 vs 78. 05 7.45 g mL-1 min , P<0.05); (5) There is no significant difference in Pharmacokinetics parameters between the middle age group and the young group , and neither is it between male and female group, P>0.05.3. The median performance error (MDPE) was - 10.75%, The median absolute performance error (MDAPE) was 8.57%, The wobble (the median absolute deviation of each PE from the MDPE) was 14.60%. The correl of two groups was 0.68.CONCLUSION1. HPLC-ECD method for determinating propofol concentration in plasma israpid ,simple, accurate and sensitive. It is suitable for monitoring propofol andpharmacokinetics study.2. In this study, the propofol metabolism in the old group is low, which indecates that it is necessary to decrease the dose in the old patients. There are no significant differences in pharmacokinetics parameters between the middle and the young group ,and neither is it between male and female.3. The performance of the TCI of propofol is acceptable for clinical use. but the propofol pharmacokinetics parameters adopted in the system are not fit for Chinese and it may be required to be optimized.
Keywords/Search Tags:propofol, plasma concentration, HPLC, pharmacokinetics, TCI
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