Dexamethasone is a synthetic glucocorticoid that is widely used in clinical due to its multiple pharmacological effects. Recently, dexamethasone is increasingly utilized in anti-cancer therapy. It is frequently used to prevent side effects of chemotherapy such as nausea, vomiting and pain, as well as to increase the anti-tumor activity of the cancer chemotherapeutic agents as a chemosensitizer and to inhibit tumor growth as an anti-cancer agent in some certain cancers. Dexamethasone produces the effects in anti-inflammation, anti-angiogenesis, control of estrogen activity and so on, by binding to glucocorticoid receptor to regulate gene expression of some important bio-signal molecules. Those signal pathways could interfere with the transcription of various factors which can regulate proliferation, invasion and metastasis of tumors.

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.

This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.

This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.

AIM To investigate the hypoglycemic effect of buccally delivered insulin solution (INS SOL) in normal rats. METHODS The hypoglycemic response was examined after buccal delivery of INS SOL co administered with various absorption enhancers. The pharmacological bioavailability (PA) was used to evaluate the absorption enhancement of INS SOL from the buccal cavity under various conditions compared with subcutaneous injection. RESULTS In the absence of enhancers, the PA was low(6 8%) after buccal delivery of INS SOL. However, the concomitant administration of sodium lauryl phosphate, sodium deoxycholate, Brij78 as well as lecithin appeared to be more effective in increasing the hypoglycemic effects of insulin. INS SOL (5 ??kg -1 ) containing 5% Brij 78 had the highest PA of 33%. CONCLUSION The use of proper absorption enhancers is useful for improving the buccal absorption of insulin.

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.

In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.

Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum concentrations data from 260 patients including 177 males and 83 females were collected separately from two centers. A one-compartment model was used to describe this sparse data. No significant difference was observed between two center datasets by introducing SID covariate. The final model was as CL= (θ (base0+ θ(max) x(1 -e(-θ(Age)(Age/72) and V = θ x θ (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the most significant covariate in the final model. Typical values of clearance (CL) and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76 L, respectively. Internal model validation by Bootstrap and NPDE were performed to evaluate the robustness and prediction of the final model. The median and 95% confidence intervals for the final model parameters were based on 1000 Bootstraps. External model evaluation was conducted using an independent dataset that consisted of 34 patients to predict model performance. Pharmacodynamic assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated by clearance based on the above population model. The results indicate that the conventional dosing regimen probably being suboptimal concentrations in aged patients. The approach via population pharmacokinetic of VAN combined with the relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational dose for attaining efficacy.

The frequency and scale of Harmful Algal Bloom (HAB) and marine algal toxin incidents have been increasing and spreading in the past two decades, causing damages to the marine environment and threatening human life through contaminated seafood. To better understand the effect of HAB and marine algal toxins on marine environment and human health in China, this paper overviews HAB occurrence and marine algal toxin incidents, as well as their environmental and health effects in this country. HAB has been increasing rapidly along the Chinese coast since the 1970s, and at least 512 documented HAB events have occurred from 1952 to 2002 in the Chinese mainland. It has been found that PSP and DSP toxins are distributed widely along both the northern and southern Chinese coasts. The HAB and marine algal toxin events during the 1990s in China were summarized, showing that the HAB and algal toxins resulted in great damages to local fisheries, marine culture, quality of marine environment, and human health. Therefore, to protect the coastal environment and human health, attention to HAB and marine algal toxins is urgently needed from the environmental and epidemiological view.
Amnesia ; chemically induced ; Animals ; China ; epidemiology ; Ciguatoxins ; toxicity ; Diarrhea ; chemically induced ; Dinoflagellida ; Environment ; Eukaryota ; chemistry ; Eutrophication ; Fisheries ; Food Contamination ; Foodborne Diseases ; epidemiology ; etiology ; Humans ; Kainic Acid ; analogs & derivatives ; poisoning ; Lethal Dose 50 ; Marine Toxins ; chemistry ; poisoning ; toxicity ; Neurotoxicity Syndromes ; etiology ; Okadaic Acid ; poisoning ; Oxocins ; poisoning ; Paralysis ; chemically induced ; Seawater ; Shellfish Poisoning

Objective To compare the cost and utility of aflibercept and ranibizumab in the treatment of diabetic macular edema(DME),in order to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods The Markov model was established by extracting the clinical medication patterns,the survival status of the two treatment regimens within 10 years were simulated,the cost and health utilities were calculated respectively,and the incremental cost-utility ratio(ICUR)was obtained.Compared with the 2022 per capita gross domestic product(GDP)of China,which was 1 time,as the willingness to pay(WTP),the cost-utility advantage scheme was selected.Results During the simulation period,the ICUR of aflibercept compared with ranibizumab was 61 024.22 yuan/quality-adjusted life year(QALY),which was lower than that of WTP,which had obvious economic benefits.Univariate sensitivity analysis showed that the metastasis probability of visual acuity improvement with aflibercept and the number of ranibizumab injections per year were important influencing factors for ICUR.Probabilistic sensitivity analysis showed that when WTP was 1 time of the GDP,aflibercept had a significant cost-utility advantage,the economic probability was 63.7%,and the results were relatively stable.Conclusion For the treatment of DME,aflibercept has a cost-utility advantage over ranibizumab.