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OBJECTIVE:To establish population pharmacokinetics(PPK)model of vancomycin so as to evaluate the effects of cystatin C(Cys C)on the pharmacokinetics parameters of vancomycin. METHODS:Totally 333 times therapeutic drug monitoring (TDM)were retrospectively collected from 225 patients who received vancomycin. Using sex,age,body weight(mT),Scr and Cys C as covariates,PPK model was established by using nonlinear mixed effect model method. Bootstrap method and normal prediction distribution error(NPDE)method were adopted for internal validation of model. Forty times of TDM data were collected from other 27 patients for external validation. Predicted accuracy and precision of model were investigated with mean prediction error (MPE) and root mean square error (RMSE). The effects of Cys C change on pharmacokinetic parameters of vancomycin were evaluated with steady state trough concentration and apparent clearance rate (CL/F) of vancomycin in typical patient (65 year-old,64 kg,Scr 66 μmol/L,1 000 mg,q12 h)forecasted with the final model at different levels of Cys C. RESULTS:CL/F of vancomycin was significantly influenced by age,body weight,the levels of Scr and Cys C. The final model was CL/F(L/h)＝3.68×(Scr/66)－0.431×(mT/64)1.1×(Age/65)－0.368×(Cys C/1.04)－0.693,V/F was equal to 82.5 L. The robust rate verified by Bootstrap method was 100%. Except for the interindividual variation of V/F,the relative bias of other pharmacokinetic parameters was less than 5%,and the estimated parameters of the final model were in the 95% confidence intervals of estimated values of Bootstrap. NPDE results showed that the homogeneity of variance was consistent with normal distribution (P＞0.05). In external validation,MPE and RMSE of the simplest model were －1.52 μg/mL and 6.87 μg/mL. MPE and RMSE of the final model were －0.32 μg/mL and 4.27 μg/mL,the accuracy and precision were improved significantly in the final model. When Cys C levle of typical patient was 0.3-4.0 mg/L,the steady state trough concentration predicted by final model were 5.25-29.97 μ g/mL and CL/F were 1.45-8.71 L/h. CONCLUSIONS:Age,body weight,the levels of Scr and Cys C significantly influence the pharmacokinetic parameters of vancomycin;moreover,the level of Cys C can change blood concentration of vancomycin. Established PPK model is of great predictive performance,which can be used to estimate the individual pharmacokinetics parameters of vancomycin.
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Objective:To investigate the correlation of the blood concentration of tacrolimus ( Tac) and serum cystatin C ( SCysC) and serum creatinine (Scr) in the patients with renal transplantation. Methods:Totally 84 cases of renal transplantation patients (67 male/17 female) treated with Tac were involved. The blood concentration of Tac, SCysC and Scr were monitored after the operation. Data results were categorized according to the postoperative time and the blood concentration. The correlations of Tac blood concentra-tion,SCysC and Scr were analyzed and compared by using Pearson correlation analysis. Results: The blood concentration of Tac was not significantly associated with SCysC and Scr in different postoperative time groups and different drug concentration groups ( P >0. 05). As the extension of time,the blood concentration of Tac showed a gradual declining trend, while SCysC and Scr levels de-creased first, and then increased gradually after two years of the operation. Conclusion:The blood concentration of Tac has no effect on the function evaluation of transplanted kidney by the biochemical indicators such as SCysC and Scr.
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Aim To investigate the mechanism of dia-betes changing the hepatic CYP1 A2 through in vitro cell culture study.Methods The function of CYP1 A2 in HepG2 and Fa2N-4 cells were evaluated by determi-ning the level of phenacetin metabolism,and the mR-NA expression of CYP1 A2 in cells was detected by real time PCR.HepG2 cells were co-cultured with serum of diabetic rats(type 1 and type 2)and normal rats,then the CYP1 A2 function in cells were evaluated.Then, the HepG2 and Fa2N-4 cells were co-cultured with a series of concentrations of saturated (including palmitic acid and stearic acid)and unsaturated fatty acids(in-cluding oleic acid and linoleic acid)for 48 h,and the function and expression of CYP1 A2 in the cells were compared.Results It was found that the activities of CYP1 A2 were higher in cells incubated with diabetic serum of both type.All high concentration of fatty acids could increase the function and expression of CYP1 A2 in both HepG2 and Fa2N-4 cells.Conclusion It is speculated that the abnormal level of fatty acids under diabetic state might be part of the reasons why diabetes change the hepatic CYP1 A2,which provides the basis for future study.
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OBJECTIVE:To investigate the function change of intestinal CYP3A4 and P-glycoprotein (P-gp) under diabetic conditions and its mechanism. METHODS:Caco-2 cells were respectively added with 25, 50 and 100 μmol/L midazolam (CYP3A4 probe substrate) for incubation for 15,30,60,120,180 min;with 0.1,0.2,0.4 μg/ml rhodamine 123 (P-gp sub-strate)for incubation for 15,30,60,90,120 min to determine the substrate concentrations and incubation time. Caco-2 cells were added with insulin,glucose and fatty acid (palmitic acid and oleic acid) at different concentrations,and then the production of 1′-OH-midazolam,the metabolite of midazolam,and the intake of rhodamine 123 were determined,in order to investigated the ef-fect on the function of CYP3A4 and P-gp. RESULTS:The optimal substrate concentrations and incubation time were as follows as 50 μmol/L midazolam,0.1 μg/ml rhodamine 123 and incubation for 2 h. With the increase in the concentration of insulin,glucose and palmitic acid,the production of 1′-OH-midazolam and the activity of CYP3A4 reduced;the intake of rhodamine 123 in-creased,and the efflux transport function of P-gp decreased. Oleic acid had no significant effect on the production of 1′-OH-mid-azolam or the intake of rhodamine 123. CONCLUSIONS:Under diabetes condition,the increase of insulin,glucose and palmitic acid may reduce the function of CYP3A4 and P-gp,while oleic acid has no effect on the function.
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OBJECTIVE:To explore the approaches for clinical pharmacists to participate in the treatment for lung cancer. METHODS:Based on the work of oncology department,the content and method of clinical pharmacist participating in clinical drug therapy were introduced in the terms of rationality,drug interaction,pain treatment,etc. RESULTS:Clinical pharmacists could participate in the treatment for lung cancer through paying attention to rationality of antitumor drug and ancillary drug use, drug interaction and pharmaceutical care for pain treatment,conducting special lecture for medical staff,and developing clinical study. CONCLUSION:Clinical pharmacists can provide various pharmaceutical care to promote safe and rational drug use.
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0.05), but significant difference when compared the older-age group with the young & middle-age group(P
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OBJECTIVE: To analyze the therapeutic drug monitoring results of valproic acid( anti- epileptic drug) . METH-ODS: The concentrations of valproic acid in 226 cases in our hospital were determined by fluorescence polarization immunoassay. RESULTS: The results showed that 47. 79% were within the normal referenced concentration range, with average concentration at( 66. 19? 12. 13) ? g? mL- 1, 46. 90% were below the lower limit and 5. 31% were above the upper limit. CONCLUS-ION: The monitoring results are far from satisfactory. It is advisable to adopt individualized administration so as to achieve the goal of treatment.
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0 05) CONCL_USION:The adsorption of infusion set will not result in obvious changes of drug concentration
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OBJECTIVE: To evaluate the effect of intervention measures on perioperative preventative application of antibiotics. METHODS: 120 surgery patients in our hospital were collected and studied comparatively before (Jul.～Dec. of 2006) and after carrying out intervention measures (Jul.～Dec. of 2008). RESULTS: The rational utilization rate of antibiotic during perioperative period increased from 0% (before intervention) to 56.7 % (after intervention). Average admission day and average medication duration after operation both were shortened (P