OBJECTIVE:To establish physiological pharmacokinetic (PBPK) model of cefdinir in healthy volunteers,and to predict pharmacokinetic process of cefdinir in volunteers after oral administration. METHODS:Using“toubao dini”“cefdinir”“logP”“pKa”as keywords,related literatures about physico-chemical constants of cefdinir were retrieved from CNKI,ScienceDi-rect,PubMed and other databases;according to related guidelines and preliminary clinical trial plan of FDA,GastroPlusTM 8.6 soft-ware was used to establish PBPK model of oral administration of cefdinir;the effectiveness of the model was evaluated by multiple error. The model was used to simulate the absorption of cefdinir in the gastrointestinal tracts. The bioequivalence of test preparation and reference preparation were evaluated through single and population(n=500)simulation tests using cmax and AUC0-∞ of cefdinir reference preparation (capsule and granular formulation) as factors when release rate t85%=15 min (i.e. accumulatively released 85% within 15 min). RESULTS:The blood concentration-time curves of cefdinir predicted by PBPK model fitted well with mea-sured value(R2≥0.95);the pharmacokinetic parameters(cmax,tmax,AUC0-∞)were close to measured results,and the multiple er-rors were less than 2. After oral administration,cefdinir was mainly absorbed by the intestinal tract (45.6%),especially by seg-ment 1 of jejunum(14.8%);the absorption amount was significantly lower than the release amount of absorption site,and reached the maximal value(about 40%)within 4 h. The results of single simulation test showed that there was no statistical significance in cmax and AUC0-∞ between cefdinir test and reference preparations (P>0.05). The results of population simulation test showed that the relative bioavailability of cefdinir test particle and test capsule respectively were 99.01%-102.99% and 97.60%-105.90%;90%CI of cmax and AUC0-∞ values were within 80%-125% of reference preparation. CONCLUSIONS:The PBPK model is accurate and reliable in this study,can provide reference for pharmacokinetic study and bioequivalence evaluation of cefdinir preparations. Test preparation and reference preparation are equivalent.

Objective To evaluate postprandial pharmacokinetics and bioequivalence of two preparations of cefdinir capsules in Chinese healthy volunteers. Methods In a two-way cross-over study, 24 healthy male volunteers were divided into two groups randomly and a single dose of cefdinir capsules of test and reference preparation were administered orally, respectively.The concentration in plasma was determined by LC-MS/MS. Pharmacokinetic parameters and bioequivalence were calculated and evaluated by DAS. Results The main pharmacokinetic parameters of test and reference were as follows: AUCt (4.35±1.09) μg??h??mL-1 and (4.12±1.22) μg??h??mL-1, AUC0-∞(4.53±1.12) and (4.53±1.73) μg??h??mL-1, t1/2 (1.74±0.29) h and (2.13±1.65) h, tmax(4.44±0.86) h and (4.54 ±1.16) h, Cmax(900±250) ng??mL-1 and (876±269) ng??mL-1 . Conclusion The test and reference preparation of cefdinir capsules are bioequivalent.

Objective: To investigate the contamination levels and dietary intakes of seven mycotoxins in Chinese diets. Methods: In Chinese Total Diet Study, food aggregation was based on the food consumption of local residents, thus generating the sampling scheme. According to the sampling scheme, the food items were sampled at three survey points in each province and then mixed in the same proportion. The mixed dietary samples were prepared after being cooked and processed. The samples comprised of 13 categories of food: cereals, beans, potatoes, meat, eggs, aquatic products, milk, vegetables, fruits, saccharides, beverages and drinking water, alcohol, and condiments. Condiments were used in cooking, so there were in total 12 varieties of samples for determination. Altogether, the study included 240 mixed dietary samples from 20 provinces with 12 varieties. The contamination levels of the seven mycotoxins, including sterigmatocystin (SMC), citrinin (CIT), cyclopiazonic acid (CPA), moniliformin (MON), gliotoxin (GLIO), mycophenolateacid (MPA) and verruculogen (Verru), were analyzed by UPLC-MS/MS method, and dietary intakes of residents were estimated as well. Results: Among the detected seven mycotoxins, MPA,GLIO and Verru were not detected. The content range of CPA in beans was 0.47-1.57 μg/kg and in alcohol was 0.19-2.26 μg/kg, and the detection rate of CPA was 7.1% (17/240). The content of SMC in aquatic products of Guangxi, in saccharides of Beijing, and in beverages of Liaoning was 2.88 μg/kg, 0.01 μg/kg, and 0.53 μg/kg, respectively. The content range of SMC in aquatic products was 0.70-1.76 μg/kg, and the detection rate was 2.9% (7/240). In addition, the content of CIT in fruit of Sichuan was 5.31 μg/kg, and the content of MON in milk of Jilin was 3.60 μg/kg. According to the dietary exposure analysis, the exposure levels of the seven mycotoxins in China's general population were low. MPA, GLIO and Verru were not detected, and the exposure range of the other four mycotoxins were 0.000-8.132 (CIT), 0.000-27.448 (SMC), 0.000-3.026 (CPA), and 0.000-62.847 ng·kg^-1·d^-1 (MON), respectively. Conclusion In the detected seven mycotoxins, CPA, SMC, CIT and MON were detected only in the individual diet in some areas with a low dietary exposure level. However, the contamination level of CPA in alcohol merits attention.

Objective: To understand the status and health risk assessment of dietary fipronil contamination among 20 provinces of China. Methods: A total of 13 kinds of dietary samples in Chinese total diet study include cereals, legumes, potatoes, meats, eggs, aquatics, dairies, vegetables, fruits, sugars, beverages and water, alcohols, condiments and their corresponding products. Among them, condiments were used in the preparation of 12 other sample categories; thus, the actual mixed dietary samples of each province covered 12 groups. A total of 240 mixed dietary samples were collected from 20 provinces in China from 2009 to 2013. After the sample extraction and cleanup, dietary samples were analyzed for the residues of fipronil and its metabolites to obtain the contamination levels of fipronil residues using liquid chromatography-high resolution mass spectrometry. The dietary intake of adult residents was estimated based on food consumption of general population of China. Results: Among the 240 dietary samples, the detection rate of fipronil was 10.4% (25 samples), and the detection rates of fipronil metabolites, i.e. fipronil desulfinyl, fipronil sulfone and fipronil sulfide were 20.4% (49 samples), 40.0% (96 samples) and 8.8% (21 samples), respectively. According to the dietary exposure analysis, the average lower and upper dietary exposure levels of fipronil residues in adult residents of China were 11.34 and 12.35 ng·kg^-1·d^-1, accounting for 5.7% and 6.2% of acceptable daily intake (ADI), respectively. The highest adult dietary intake of fipronil residues was found in Hunan province, with a value of 72.98 ng·kg^-1·d^-1, accounting for 36.5% of ADI. Vegetables were the main dietary source of fipronil residues, which contributed to 71.0% of the total intake dose. Conclusion Fipronil residues were detected in varying degrees in dietary samples, yet the health risk caused by the dietary intake of adult residents among 20 provinces of China is low.

OBJECTIVE To investigate and analyze the operational costs and current charging policies of pharmacy intravenous admixture service （PIVAS） in China， and provide a reference for promoting high-quality and sustainable development of PIVAS. METHODS Questionnaires were distributed in 30 provinces， autonomous regions， and municipalities across the country through the “Wenjuanxing” platform from May 6th to July 1st， 2022. The operational costs， charging status and suggestions of PIVAS were investigated and analyzed. RESULTS A total of 761 PIVAS participated in the survey nationwide， including 666 tertiary medical institutions， 93 secondary medical institutions， and 2 primary medical institutions. Approximately 60.58% of PIVAS had implemented a charging system that allowed charges. Among them， most PIVAS required inspection and evaluation before charging. The annual operating cost of PIVAS in China was approximately 2 098 100 yuan， with the integrated operating cost comprising 89.36% of the total， while the dispensing cost accounted for only 10.64%. Human costs emerged as the highest annual consumption （74.20%）， followed by decoration and facility maintenance costs （4.77%） and equipment acquisition costs （3.44%）. Regarding charges for different drugs nationwide， common drugs had an average charge standard of 4.39 yuan per bag while antibacterial drugs averaged 5.01 yuan per bag； hazardous drugs had an average charge of 23.17 yuan per bag， whereas parenteral nutrition solutions averaged 38.75 yuan per bag. However， the recommended average charges of the four drugs mentioned above were 6.71， 9.63， 38.35 and 44.03 yuan per bag， respectively. CONCLUSIONS At present， there is no unified inspection and evaluation standard and charging standard in China. Moreover， the current charging standard is lower than the recommended standard. It is necessary to combine operational costs and develop more reasonable and fair charging standards.