The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.
Algorithms ; Bayes Theorem ; Carbamazepine ; analogs & derivatives ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Regression Analysis ; Tacrolimus ; pharmacokinetics

Chromatography, Gas ; Humans

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.

OBJECTIVE:To study the time-concentration curves of single dose of ambroxol hydrochloride orally integrating tablets in healthy volunteers and to evaluate its bioequivalence.METHODS:A single oral dose of 90mg ambroxol hydrochloride orally dissolving tablets and 90 mg ambroxol hydrochloride tablets were given to 18 healthy volunteers by a randomized crossover design.The concentrations of ambroxol hydrochloride in plasma were determined by HPLC.RESULTS:The main pharmacokinetic parameters of the test and references preparations of ambroxol hydrochloride were as follows:Cmax were(169.58?39.43)ng?mL-1 and(170.28?43.26)ng?mL-1;tmax were(1.6?0.5)h and(2.2?0.6)h;t1/2 were(6.77?2.04)h and(6.50?1.27)h;AUC0～24 were(1 131.26?289.36)ng?h?mL-1 and(1 191.54?270.17)ng?h?mL-1;AUC0～∞ were(1 215.27?306.56)ng?h?mL-1 and(1 281.44?291.51)ng?h?mL-1,respectively.The relative bioavailability of the test preparation was(95.5?15.6)%.CONCLUSION:The result demonstrated that the two preparatioins were bioequivalent in absorption degree,suggesting the rapid release characteristics of the preparation.

China ; epidemiology ; Humans ; Occupational Diseases ; epidemiology ; prevention & control ; Surveys and Questionnaires ; Trimethyltin Compounds ; analysis ; poisoning

OBJECTIVE:To achieve the drug intelligent supervision in transportation within hospital and storage process,and promote quality safety of drugs. METHODS:The function and operation of Radio frequency identification(RFID)medicine logis-tic box was introduced,its application in one year in inpatient pharmacy of our hospital since Sept. 2013 was summarized,and its application effect and deficiency were analyzed. RESULTS:RFID medicine logistic box showed heat preservation and locking func-tions,which can be used for the cold-chain medicine and lock packing transportation for the ward. It can achieve information bind-ing after connecting with corresponding platform,record real-time record temperature,logistic box opening and closing information and data,as well as a variety of ways to alarm by SMS and mail,etc. However,failed login server and unpacking caused by unsta-ble wireless signals were found when applying the box,also drug damage and other defects were caused by unreasonable box struc-ture. And the daily average incidence dropped from the initial period (Nov. 2013) 11.9 times (cases) to the late period (Sept. 2014) 3.3 times (cases) after continuous improvement. CONCLUSIONS:Applying of medicine logistic box can strengthen cold-chain transport integrity and regulatory information in our hospital,ensure the safety of drug transport and query traceability of information.

Air ; analysis ; Chromatography, Gas ; methods ; Ethylene Oxide ; analysis ; Furans ; analysis ; Methylene Chloride ; analysis ; Workplace

Objective - （ ） To analyze the epidemiological characteristics of occupational noise induced deafness ONID （ ） diagnosed by Guangdong Province Hospital of Occupational Disease Prevention and Control GDHOD from 2016 to 2020 and - Methods the reasons non ONID diagnosis. The data of ONID patients diagnosed in GDHOD from 2016 to 2020 were collected “ from the Occupational Disease Report Card in the Occupational Disease and Occupational Health Information Monitoring ” “ ” - System subsystem of the China Disease Prevention and Control Information System . The data of non ONID subjects were ， collected from the occupational disease diagnosis archives in the same hospital and the relevant data were analyzed Results ， ， （ ） retrospectively. Of the 1 432 subjects 824 subjects were diagnosed as ONID patients mainly of mild ONID 86.0% . （M） ， M Male patients accounted for 88.0%. The median of diagnosis age was 45.0 years old and of length of employment of ， ， ， diagnosis was 8.3 years. ONID patients were mainly found in Zhongshan Dongguan Zhuhai Jiangmen and Guangzhou City in ， ， （ ） the Pearl River Delta accounting for 67.6%. The cases distributed in 519 enterprises mainly on manufacturing 90.2% . ， - ， ； Among the 139 enterprises each enterprise had 2 11 patients worked within five years accounting for 53.9% 91.1% of the -， - - - ONID patients were distributed in large medium and small enterprises. ONID patients mainly worked in non public enterprises that accounted for 91.3%. There were 606 subjects could not be diagnosed as ONID. The main reasons for not being （ ）， diagnosed were that the weighted value of better ear hearing threshold was less than 26 dB 34.8% the working history of （ ）， occupational noise exposure was less than three years 31.5% the weighted value of better ear hearing threshold was less thanConclusion 26 dB and the average hearing threshold of binaural high frequency was less than 40 dB 16.2% . The ONID ， ， -， - patients have the characteristics of group aggregation. The Pearl River Delta manufacturing industry large medium and - - ： small non public enterprises are the key points of ONID prevention. The main reasons for not being diagnosed as ONID were ， the working history of occupational noise exposure was less than three years the weighted value of better ear hearing threshold ， - was less than 26 dB and the average high frequency hearing threshold of both ears was less than 40 dB.

Objective: To observe the level of pro-opiomelanocortin (POMC) mRNA expression in the hypothalamic arcuate nucleus in young and senile rats. Methods: POMC mRNA was determined with in situ hybridization, the hybridization signals and areas of POMC mRNA-positive cells were measured with computer image analysis system. Results: Compared with young rats, average gray values of POMC mRNA-positive neurons in the hypothalalmic arcuate nucleus and near region in the senile rats decreased, but the numbers of POMC mRNA-positive neurons did not change significantly. Conclusion: The decrease of POMC mRNA expression level in individual neurons in hypothalamic arcuate nucleus of senile rats is one of the causes that decrease the expression of peptides-derived from POMC gene.

Objective To observe the clinical effect of pneumatically ballistic extracorporeal shockwave on chronic nonspecific low back pain. Methods 66 cases with chronic nonspecific low back pain were randomly divided into treatment group (n=33) and control group (n=33). There were 1 case drop-out in the treatment group and 2 in the control group. The treatment group accepted pneumatically ballistic extracorporeal shockwave, and the control group accepted hot magnet for 2 weeks. They were assessed with Visual Analogue Scale (VAS) and Finger-floor Distance (FFD) before and after treatment. Results The scores of VAS and FFD improved in both groups after treatment (P<0.05), and the difference before and after treatment were more in the treatment group than in the control group (P<0.05). Conclusion The pneumatically ballistic extracorporeal shockwave is more effective on chronic nonspecific low back pain than hot magnet.