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Objective To compare the accuracy of Marsh model and Schnider model for propofol target?controlled infusion ( TCI) system. Methods Eighty patients, aged 20-60 yr, of American Society of Anesthesiologists physical status ⅠorⅡ, with body mass index of 17?5-28?0 kg∕m2 , scheduled for e?lective gynecological operation under general anesthesia, were equally and randomly divided into either Marsh model group ( group M) or Schnider model group ( group S) using a random number table. The target plasma concentration was set at 3 μg∕ml in both groups. During TCI and at different time points after the end of TCI, the blood samples were collected for determination of blood propofol concentrations by high per?formance liquid chromatography with fluorescence detector. The difference between measured and predicted concentrations (△C) at each time point was calculated. The median performance error ( MDPE) , median absolute performance error ( MDAPE) , and wobble of propofol TCI system were calculated in each group. Results In M and S groups, the MDPE was 9. 90% and 14?00%, respectively; the MDAPE was 11?43% and 14?49%, respectively;the wobble was 7?77% and 7?79%, respectively. There was no sig?nificant difference in △C at each time point during TCI between group M and group S (P>0?05). After TCI was stopped, △C at each time point was significantly lower in group M than in group S ( P<0?05) . Conclusion Marsh model provides higher accuracy than Schnider model for propofol TCI system in the pa?tients undergoing gynecological operation.
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The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.
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The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.
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OBJECTIVE:To investigate the compatible stability of isosorbide mononitrate(ISO) and dopamine(DA) hydrochloride in glucose injection.METHODS:The contents of ISO and DA in the mixture of ISO and DA at 20 ℃ and 30 ℃ under natural illumination within 24 h,and the pH and appearance of the mixture were monitored.RESULTS:No significant change was noted in the concentrations of ISO and DA,the pH and the appearance of the mixture at 20 ℃ or 30 ℃.CONCLUSION:The mixture of ISO and DA in glucose injection was stable at 20 ℃ or 30 ℃,but which should be used up within 18 h after mixing.
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Purpose The aim is to establish the HPLC method for the determination of Fluoro-deoxyuridine in plasma.Methods The Chromatography conditions include: Chromatography column: Nova-pak C18(3.9mm×150mm,4μm), mobile phase: 0.05mol/L sodium phosphate monobasic -methanol-water(0.5∶7∶92.5)， UV detection at 260nm， FUDR was extracted with ethyl acetate. Results The average recoveries were 96.4%，96.5%，97.8% for concentration 0.23、1.67、20.0μg/ml (n=5).The corresponding reproducibility were RSD 1.61%, 1.98%, 3.17% respectwely for iner-day and RSD 3.56%, 1.90%, 2.63% for the intra-day(n=5). The FUDR concentration was linear with a correlation coefficient of 0.999 4 over the range of 0.099～20.0μg/ml. Conclusion The method was sensitive and accurate and suitable for pharmacokinetics and bioavailability study of FUDR.
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OBJECTIVE:To study the compatible stability of gatifloxacin for injection with tinidazole injection.METHO_DS:Contents changes of gatifloxacin and tinidazole within 48h after mixing were determined by HPLC;and the appearance,pH value were observed and determined.RESULTS:The contents changes for both gatifloxacin and tinidazole were less than 5%. The mixed solution was clear in appearance yet without generation of gas and sediments.No significant changes were noted in pH value,color and smell.CONCLUSION:The mixed solution of gatifloxacin for injection with tinidazole injection is stable at room temperature within 48h and which can be applied in combination.