Research progress on individualized administration of linezolid based on population pharmacokinetics / 中国药房

Linezolid is an antibacterial agent for the treatment of multi-resistant Gram-positive bacterial infections， which is widely used in clinical practice. However， there are large individual differences in the pharmacokinetic characteristics of the drug in patients， and it is difficult to obtain the optimal therapeutic effect when the drug is administered according to the conventional dose in the instructions. Therefore， it is necessary to carry out therapeutic drug monitoring （TDM） for linezolid， and guide and optimize its antibacterial treatment plan by using population pharmacokinetics （PPK） and pharmacodynamics principles. This paper summarizes the PPK changes and the research progress of individualized administration of linezolid in various populations， and recommends that the patient’s steady-state blood concentration is kept at 2-8 mg/mL through TDM when using linezolid clinically. It is recommended to appropriately reduce the dosage for patients with liver and kidney dysfunction， appropriately increase the dosage for obese， burned and children patients， and provide pharmaceutical monitoring during the medication process to promote rational drug use.

Therapeutic drug monitoring in the individualized administration of cyclosporin A: Application and research progress / 中国临床药理学与治疗学

Cyclosporine A (CsA) is a kind of cellular immunosuppressant, which is widely used in organ transplantation, blood diseases and autoimmune diseases. Because of its poor oral bioavailability, individual differences and prone to adverse reactions, so clinical therapeutic drug monitoring (TDM) and individual administration of CsA can ensure its safety and effectiveness. However, the treatment window of CsA is narrow, and its blood concentration is affected by age, sex, diet, drug factors, genetic factors and so on. Therefore, combined with the literature reports at home and abroad, this paper reviews the research on the application of TDM and individual drug administration of CsA, in order to provide more valuable reference for clinical safe and rational drug use.

The principle of drop-on-powder 3D printing and its application and challenge in solid preparation / 药学学报

3D printing technology has the advantages of accurate spatial distribution, accurate drug release and personalized drug dosage, which can make up for the shortcomings of traditional pharmaceutical technology. In recent years drop-on powder (DoP) 3D printing technology has been widely used in pharmaceutical preparation. Compared with other types of 3D printing technology, it is more simple, flexible and easy to operate. In 2015, Aprecia Pharmaceuticals announced that the US Food and Drug Administration (FDA) approves the launch of its first instant tablet Spritam® (levetiracetam) made with DoP 3D printing. After the first 3D printed medicine was launched, people also saw the unique advantages and broad prospects of DoP 3D printing technology platform in pharmaceutical preparation. This review focuses on the technical principles and key factors of DoP 3D printing, its application in the preparation field and its future development challenges.

A Case Discussion of Individualized Administration of Warfarin by Maximum a Posteriori Bayesian Estima-tion Method / 中国药师

Objective:To explore the role played by clinical pharmacists in the formulation and pharmaceutical care of individual-ized administration of warfarin. Methods:Clinical pharmacists adopted maximum a posteriori Bayesian method to formulate the dosage regimen of patients treated with warfarin and monitored the implementation process. The increase of INR was timely identified on ac-count of drug interactions to avoid bleeding events,as well as the decrease of INR caused by patients' medication mistakes to avoid re-currence of thrombosis. Results:The maximum a posterior Bayesian estimation method could be used to estimate and guide clinical medication,which showed great reference value for individualized drug regimen. Conclusion:Clinical pharmacists should formulate in-dividualized administration plan according to genetic testing results and choose optimal treatment for patients. Moreover,the implemen-tation of dosage regimen should be monitored during the whole progress,so as to timely find INR abnormal fluctuations due to disease interactions,drug interactions,poor treatment compliance and so on,and consequently improve anticoagulant effect and reduce adverse reactions such as bleeding and thrombosis etc.

Research progress on clinical gene polymorphism of clopidogrel resistance / 中国药学杂志

Clopidogrel plays an important role in anti-platelet aggregation, especially in acute coronary syndrome and percutaneous coronary intervention. However, clopidogrel resistance is common in clinical treatment. There are many factors response to clopidogrel resistance.Current researches concentrated in CYP450 enzyme gene polymorphism with clopidogrel resistance. There are few reviews on genetic polymorphisms of transporter and receptor binding sites, furthermore, the gene polymorphisms among different ethnic groups in plateau populations are very rare. In this paper, we mainly reviewed the relationship between gene polymorphism of drug-transporter and bioavailability of clopidogrel, the whole process of drug-metabolizing enzyme′s bioconversion of clopidogrel and the active metabolite of clopidogrel combine with the receptors.A mutation in the ABCB1 gene of the transporter was found to affect the bioavailability of clopidogrel. The key role of polymorphisms in the metabolic enzyme gene is CYP2C19 and CES1. The dose should be adjusted according to genotyping. The biologically active gene P2Y12 polymorphism affects the efficacy of clopidogrel. Therefore, understanding the clopidogrel gene polymorphism influencing factors can help individualized administration of clopidogrel to minimize thrombotic events caused by insufficient antiplatelet effect or hemorrhagic events caused by excessive anti-platelet effect.

Analysis of Population Pharmacokinetics of Vancomycin Using Cystatin C as a Marker of Renal Function / 中国药学杂志

OBJECTIVE: To establish a population pharmacokinetics(PPK) model of vancomycin in adult patients and investigate the factors influencing vancomycin clearance.METHODS: The nonlinear mixed-effect model(NONMEM) was used to investigate the population characteristics of vancomycin in adult patients and the serum cystatin C was used as a marker of renal function. The final model was built by forward inclusion approach and backward elimination method. Fitting effect of the model was evaluated by the goodness of fit plots(GOFs). Nonparametric Bootstraps and normalized prediction distribution errors(NPDE) were performed to evaluate the robustness and predictive efficacy of the final model. External model evaluation was conducted using an independent dataset to evaluate the model predictability. RESULTS: Vancomycin PPK model was set up via 147 serum trough concentration data from 95 adult patients. The estimated population typical values of clearance rate and apparent volume of distribution were 3.57 L·h-1 and 63.30 L, respectively. The main factor influencing clearance was renal function. The GOFs showed that the final model was stable and effective, and the fitting degree of the final model was better than that of the base model. The robust rate verified by Bootstrap was 99.45%. All of the relative biases between the median of parameters validated by Bootstrap and the estimated parameters of final model were within ±3%, and the 95% confidence intervals of these validated parameters did not include zero. The NPDE followed the N(0,1) distribution with a global adjust P value of 0.334, which indicated that the model had a high predictive accuracy. External evaluation was performed via an independent dataset of 40 concentration data from 20 patients. The mean prediction error(MPE) and mean absolute prediction error(MAPE) based on population predictions(PRED) was -1.90% and 24.34%, respectively. CONCLUSION: Vancomycin PPK model established in the study is of as a good stability and high predictive accuracy, as a reference for developing individualized administration regimens.

Analysis of Anticoagulation Effects and Influential Factors of Warfarin on the Lower Extremity Deep Ve-nous Thrombosis / 中国药房

OBJECTIVE:To investigate the anticoagulation effects of warfarin on the lower extremity deep venous thrombosis (LEDVT),and to analyze its influential factors,in order to provide scientific basis for individualized medication of warfarin in the clinic. METHODS:Totally 140 cases of LEDVT were selected and treated with warfarin on the and day after admission with initial dose of 5.0 mg,qd,2.5 mg for following 2 days,orally,qd. The dose of warfarin was adjusted 72 h after medieation according to INR of patients. The dose of warfarin wasused as the maintenance dose when INR reached the anticoagulant target. Clinical data of patients were recorded,and blood biochemical indexes and coagulation function were detected. The influential factors of anticoagu-lation effects were analyzed by multiple-linear regression. At the same time,the results of INR were recorded before medication and 24,48,72 h after medication. RESULTS:INR of patients receiving warfarin had the potential to increase,compared to before medication;24,48,72 h after medication,INR value showed a gradual upward trend,without statistical significance(P>0.05). The change of INR within 24 h after medication was less than that within 24-48 h after medication;the change of INR within 24-48 h after medication was less than that within 48-72 h after medication,with statistical significance (P<0.01). The influence of various factors on the anticoagulant effect of warfarin in descending order was as follows:age,weight,low density lipoprotein cholesterol,plasma albumin,disease duration. Among them,age and low density lipoprotein cholesterol were positively correlated with anticoagulation,while body weight,plasma albumin and disease duration were negatively correlated with anticoagulation. CONCLUSIONS:Both age and body weight are the main influential factors for anticoagulation effect of warfarin. Individualized medication should be implemented in order to improve the anticoagulation effects of warfarin.