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This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmacometrics approaches including QSP, PK/PD, dose response analysis, MBMA, in dose-response, preclinical and clinical translation, and correlation between biomarkers and efficacy of vaccines. It is expected that the successful application of model informed drug development can promote model informed vaccine development so that pharmacometrics makes its due contributions to the development of safer, more effective and more controllable vaccine products.
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Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.
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With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.
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Objective To explore the mechanism of tripterygium wilfordii polyglycoside tablets for elderly patients with relapsing refractory immune thrombocytopenic purpura (ITP),and to seek the theoretical basis for Chinese medicine treatment of this disease.Methods The clinical data of 79 patients with relapsing refractory ITP were retrospectively analyzed.According to whether the combined use of tripterygium wilfordii polyglycoside,they were divided into the control group (35 cases) and the observation group (44 cases).The control group was treated with platelet and tranexamic acid,sulfasalazine,sulforaphane sodium,hemagglutinin and other symptomatic hemostasis treatment.The observation group in symptomatic hemostasis support on the basis of treatment with tripterygium wilfordii polyglycoside tablets.The CD4+/CD8+ ratio and CD4+ CD25+ Treg expression were compared between the two groups.Results The CD4+/CD8+ ratio,CD4+ CD25+ Treg and platelet count in the control group before treatmentwere (0.96 ± 0.36),(1.21 ± 0.67) ％,(13.14 ± 6.92) × 109/L,respectively,which of the observation group were (0.92 ± 0.37),(1.19 ± 0.59) ％,(11.51 ± 6.21) × 109/L,respectively,there were no statistically significant differences between the two groups (all P ＞ 0.05).The CD4+/CD8+ ratios in peripheral blood of the observation group at 2 weeks,3 weeks and 4 weeks after treatmentwere (1.04 ±0.56),(1.55 ±0.34),(1.59 ±0.41),respectively,there were statistically significant differences between the two groups (t =9.994,9.797,all P ＜ 0.05).The CD4+ CD25+ Treg proportions in the observation group at 2 weeks,3 weeks and 4 weeks after treatmentwere (1.01 ± 0.61) ％,(1.06:±:0.57) ％,(5.92 ± 0.65) ％,respectively,there was statistically significant difference between the 4 weeks after treatment and before treatment(t =5.378,P ＜ 0.05).The CD4+/CD8+ ratios in the peripheral blood of the control group were (1.01 ±0.60),(0.89 ±0.50) and (0.96 ±0.51),respectively,and the CD4+ CD25+ Treg in control group at 2 weeks,3 weeks and 4 weeks after treatment proportions were (0.99 ±0.72)％,(1.15 ±0.66)％,(1.22 ±0.56)％,respectively,there were no statistically significant differences between before and after treatment (all P ＞0.05).There were statistically significant differences in the CD4+/CD8+ ratio and CD4+ CD25+ Treg expression between the observation group and control group at 4 weeks after treatment (t =8.589,P ＜ 0.01;t =2.369,P ＜ 0.05).There was no statistically significant difference in the platelet count between the two groups(P ＞ 0.05),but the symptoms of bleeding of the observation group was lighter at 3 weeks after treatment.Conclusion Tripterygium wilfordii polyglycoside improves the expression of CD4+/CD8+ and CD4+ CD25+ Treg in peripheral blood of elderly patients with relapsed or refractory ITP.It is an ideal drug for the treatment of relapsed and refractory ITP in the elderly,it is worth further study.