Feature Of Pharmacokinetics Of Propofol In Patients Of Different Gender Under General Anesthesia

Background and ObjectivePropofol (2,6-2-isopropyl phenol) is a new type of rapid onset, short-acting intravenous general anesthesia drugs, waking up quickly and completely, with a continuous infusion of no accumulation phenomenon, so that other intravenous general anesthetic can not compare. So now generally it is used for anesthesia induction, anesthesia maintenance, and also commonly used in local anesthesia, after the surgical operation, ICU ward, and sedation.Although there are many studies on the pharmacokinetics of propofol at home and abroad, there is a large deviation in these studies. In recent years, with the development of molecular biology and biochemistry, as well as the continuous in-depth study of animal experiments, many studies confirm gender differences effect on the pharmacokinetics of drugs in a wide range. Pharmacokinetics of drugs have very important influence on toxicology and pharmacodynamic, while the impact of gender differences is an important factor in pharmacokinetics. Therefore, gender differences should be given full attention in order to maximize the effectiveness and safety of drugs, and at the present there is not yet study on effects of gender on pharmacokinetics of propofol. Therefore, the purpose of this study is to observe the Effect of gender on pharmacokinetics of propofol in abdominal surgery patients under general anesthesia and to achieve reasonable safety for clinical anesthesia drugs provide a theoretical basis.Materials and MethodsSelecting abdominal surgery patients will undergo general anesthesia of 20 cases, ASAⅠ～Ⅱ, divided into male group (48～59 years) and female group (42～59 years) by sex,10 cases of each group. physical examination of preoperative showed no abnormality. After the patient going the operating room, opening venous channel, and the induction of anesthesia before the infusion of 0.9%Nacl 10～15 ml·kg-1, the start of intravenous induction of anesthesia with propofol 2 mg·kg-1 (in the 20s within a constant speed to push), remifentanil 1.5μg·kg-1 (60s within a constant speed of infusion) and succinylcholine chloride 1.5mg·kg-1, skilled anesthetists perform endotracheal intubation. Surgery with isoflurane (1%～2%) plus nitrous oxide (N2O: O2=1:1) inhalation anesthesia was maintained with remifentanil 0.2～0.3μg·kg-1 continuous infusion, depending on the depth of anesthesia to adjust the maintenance dose to ensure that patients maintain a more stable vital signsAfter Propofol injection, take blood samples 3ml through the subclavian vein before (Omin) and 1,2,3,4,6,10,15,30,45,60,90,120,180,240,360,720min after injection. After 3000r/min centrifugal plasma lOmin, shifted to 2mlEP the upper tube, and stored at -80℃refrigerator. Using high performance liquid chromatography to detect blood concentration of propofol.Data of propofol plasma concentration in this study was used math-ematics by the Chinese Pharmacological Society prepared by the commission 3P97 pharmacokinetic software processing, and select the best compartment model, drawing blood drug concentration-time curves.Data was used SPSS13.0 statistical package, which resulted in using mean±standard deviation (x±s); propofol standard curve regression equation using linear regression and correlation processing, amount of data used by two independent groups t test; multiple independent quantitative single factor analysis of variance data do not meet the normal distribution using K-W tests, test standards for theα=0.05. Results1. General state of patientsTwo groups of patient's age, weight, medication, operative time, blood loss and fluid volume and others have no significant difference between the groups (P>0.05); There was no statistically significant difference (P>0.05) between the two groups of patients with livers and kidney's function and other laboratory.2. Propofol concentration in plasma with the method of high performance liquid chromatographicStandard chromatograms suggest that propofol and internal standard are completely separated, their retention times were 11.1min and 7.1min. Propofol concentration detection range is 0.04～25μg. ml-1; the minimum detection limits of propofol is 0.01μg.mL-1. With three concentrations of propofol 0.1,1 and 25μg.ml-1 detection rate, respectively 99.2%,106.9% and 98.2%, RSD<5%; propofol determination day and inter-day precision RSD 1.36% 2.46% 2.26% 4.41%.3. Two groups of patients with plasma concentrationsTwo groups of patients The blood concentration of women less than men (P <0.05) with less than 10min of two groups of patients; 10min subsequent time points plasma concentrations of women less than men, but the difference was not statistically significant (P>0.05).4.Pharmacokinetic parameters of two groups of patientsTwo sets of blood drug concentration-time data by 3P97 software curve fitting and model identification, are in line with the two compartment open model features. Two groups of male and female patients with primary pharmacokinetic parameters: T1/2pi (1.60±0.40vs1.72±0.66) min, T1/2α(20.77±7.24vs23.46±4.74) min, T1/2β(274±141vs269±155) min, AUC0→t(170.7±14.5vs170.4±17.3)μg·min-1·ml-1, CL(15.7±3.9vs18.3±4.1) ml·kg-1·min-1, VC(0.18±0.03 vs 0.21±0.03) L·k g-1, K12(0.25±0.08vs0.27±0.11) min-1, K21(0.11±0.02vs0.11±0.02) min-1, K13 (0.100±0.022vs0.097±0.025) min-1, K31(0.092±0.016vs0.102±0.0015) min-1, K10 (0.092±0.016vs0.102±0.015) min-1. In which women have a greater volume of distribution than men (P<0.05); propofol clearance rate of women larger than men (P <0.05).Conclusion1. High performance liquid chromatography for determination of plasma blood concentration of propofol by, is a simple, reliable, accurate, reproducible method, which can be used in clinical blood propofol concentration monitoring and pharmacokinetic studies.2. After a single intravenous injection of propofol 2mg.kg-1 of two groups of patients, the blood concentration of women lower than men patients; propofol concentration-time of two groups curve three compartment model, two propofol drug-time the curves meet the three-compartment model, the central compartment distribution volume (Vc) and propofol clearance (CL) of female patients larger than men.3. Sex on the single intravenous injection of propofol with propofol pharmacokinetic characteristics have significant effects.