The objective of this study is to compare the normalized prediction distribution errors (NPDE) and the visual predictive check (VPC) on model evaluation under different study designs. In this study, simulation method was utilized to investigate the capability of NPDE and VPC to evaluate the models. Data from the false models were generated by biased parameter typical value or inaccurate parameter inter-individual variability after single or multiple doses with the same sampling time or multiple doses with varied sampling time, respectively. The results showed that there was no clear statistic test for VPC and it was difficult to make sense of VPC under the multiple doses with varied sampling time. However, there were corresponding statistic tests for NPDE and the factor of study design did not affect NPDE significantly. It suggested that the clinical data and model which VPC was not fit for could be evaluated by NPDE.

Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathe-matical and statistical methods to characterize,understand,and predict a drug's pharmacokinetic,phannacodyna-mic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.

Objective To compare the diuretic efficacy of torasemide as a 2-hour continuous infusion and as a bolus injection of equal dose in patients with nephrotic syndrome,and to investigate a preferable administration mode of torasemide for these patients.Methods Twenty-three hospitalized patients were randomized to receive torasemide 20 mg or 40 mg per day by either 2-hour intravenous infusion or bolus injection,and interchanged after 48 hours of washout.Results Patients received torasemide by 2-hour intravenous infusion exhibited significantly higher daily urinary volume,chloride excretion,sodium excretion and fractional excretion of sodium (FENa) within 24 hours than those by bolus injection (P ＜ 0.05).Significantly lower bound-state torasemide excretion,higher ratio of urinary volume to torasemide excretion and a markedly larger area under the curve in the plasma concentrationtime profiles were also observed in the infusion group (P ＜ 0.05).Conclusion 2-hour continuous infusion delivers a better diuretic effect compared with a bolus injection of equal dose of torasemide in patients with nephrotic syndrome.

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.

Objective To study correlation between serum 25 (OH) d level and metabolic indexes in elderly patients with diabetes mellitus. Methods In this prospective study, 315 elderly patients with diabetes who were diagnosed and treated in our hospital from January 2018 to June 2020 were selected as the research objects, and 100 healthy volunteers in the same period were selected as the control group. The blood lipid, fasting blood glucose (FPG), fasting insulin (fins), glycosylated hemoglobin (HbA1c) and insulin resistance (HOMA) of the two groups were analyzed- The levels of FPG, fins, GHbA1c, HOMA-IR and homa-is in patients with 25 (OH) D deficiency of different severity were compared, and the correlation between serum 25 (OH) d level and metabolic indexes was studied. Results The serum 25 (OH) d level of the observation group was significantly lower than that of the control group (t = 6.080, P = 0.000); the FPG (t = 14.708, P = 0.000), GHbA1c (t = 7.165, P = 0.000), HOMA-IR (t = 8.880, P = 0.000) of the observation group were significantly higher than those of the control group, homa-is (t = 120.847, P = 0.000), fins (t = 120.847, P = 0.000)= The levels of FPG (F = 12.334, P = 0.000), fins (F = 11.897, P = 0.000), GHbA1c (F = 10.090, P = 0.000), HOMA-IR (F = 11.232, P = 0.000) and homa-is (F = 9.009, P = 0.000) were not significantly different between the two groups (P < 0.05) FPG, GHbA1c, HOMA-IR of patients from high to low were deficiency group, deficiency group and sufficiency group, fins, homa-is levels from high to low were sufficiency group, deficiency group and deficiency group; through correlation analysis, serum 25 (OH) d levels of patients were negatively correlated with FPG, GHbA1c, HOMA-IR, and positively correlated with fins, homa-is. Conclusion The level of serum 25 (OH) d in elderly patients with diabetes is significantly correlated with metabolic indexes, which can become one of the important evaluation indexes of treatment effect in the future.