A simple and sensitive HPLC-MS/MS assay for the quantitation of montelukast in cell-based systems in vitro pulmonary drug permeability study.

Montelukast is a potent and selective antagonist of the cysteinyl leukotriene receptor 1 subtype (CysLT1) and widely used in the form of oral tablets and granules for asthma prophylaxis and treatment. Recently, due to the pulmonary inhaled administration can limit montelukast distribution in the systemic circulation, avoid the first-pass metabolism and have better therapeutic effects in respiratory disease treatment, explore alternative routes of administration, like delivery of montelukast via an inhaled, is a new research trend for montelukast. The aim of the current study was to develop and validate a simple, accurate, highly sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for determination of montelukast in an in vitro cell-based pulmonary pharmacokinetics system model, which can be used to be a better understanding the fate of inhaled montelukast in the lungs. In this study, montelukast was extracted by protein precipitation with acetonitrile containing labeled montelukast. The chromatography was performed on an Agilent Eclipse plus C8 column (4.6 mm × 100 mm, 3.5 µm, Darmstadt, Germany) operating at 35 ◦C. The mobile phase consisted of acetonitrile: 20 mM ammonium formate buffer (80: 20, v/v), was delivered at a flow rate of 0.5 mL/min. montelukast and the internal standard were both eluted at 4.2 min. A linear (1/x2) relationship was used to perform the calibration over an analytical range from 0.5 to 600 ng/mL. The intra- and inter-batch precision expressed as CV for four QC samples including LLOQ range from 1.14 % to 6.25 %. The intra- and inter-batch accuracy for four concentrations of montelukast were in the range of 95.19%-104.1%. All the values for accuracy and precision were within the acceptance range. The method met all the bioanalytical method validation requirements by ICH and was suitable for the assay of montelukast which in the in vitro cell-based pulmonary pharmacokinetics system model.

Effect of venlafaxine dosage, valproic acid concentration, sex, and age on steady state dose-corrected concentrations of venlafaxine and O-desmethylvenlafaxine: A retrospective analysis of therapeutic drug monitoring data in a Chinese population.

PURPOSE: This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady-state dose-corrected serum concentrations (C/D) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV). METHODS: A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. RESULTS: We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33-59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2-fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. CONCLUSION: Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy.

A Retrospective Analysis of Steady-State Olanzapine Concentrations in Chinese Patients Using Therapeutic Drug Monitoring: Effects of Valproate and Other Factors.

BACKGROUND: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. METHODS: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated. RESULTS: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = -0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations. CONCLUSIONS: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.

Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy.

Lamotrigine (LTG) is a second-generation anti-epileptic drug widely used for focal and generalized seizures in adults and children, and as a first-line medication in pregnant women and women of childbearing age. However, LTG pharmacokinetics shows high inter-individual variability, thus potentially leading to therapeutic failure or side effects in patients. This prospective study aimed to establish a population pharmacokinetics model for LTG in Chinese patients with epilepsy and to investigate the effects of genetic variants in uridine diphosphate glucuronosyltransferase (UGT) 1A4, UGT2B7, MDR1, ABCG2, ABCC2, and SLC22A1, as well as non-genetic factors, on LTG pharmacokinetics. The study population consisted of 89 patients with epilepsy, with 419 concentrations of LTG. A nonlinear mixed effects model was implemented in NONMEM software. A one-compartment model with first-order input and first-order elimination was found to adequately characterize LTG concentration. The population estimates of the apparent volume of distribution (V/F) and apparent clearance (CL/F) were 12.7 L and 1.12 L/h, respectively. The use of valproic acid decreased CL/F by 38.5%, whereas the co-administration of rifampicin caused an increase in CL/F of 64.7%. The CL/F decreased by 52.5% in SLC22A1-1222AA carriers. Patients with the ABCG2-34AA genotype had a 42.0% decrease in V/F, whereas patients with the MDR1-2677TT and C3435TT genotypes had a 136% increase in V/F. No obvious genetic effect of UGT enzymes was found relative to the concentrations of LTG in Chinese patients. Recommended dose regimens for patients with different gene polymorphisms and comedications were estimated on the basis of Monte Carlo simulations and the established model. These findings should be valuable for developing individualized dosage regimens in adult and adolescent Chinese patients 13-65 years of age.

Forecasting incidence of extended spectrum β-lactamases-producing Escherichia coli by multiple seasonal ARIMA model / 预防医学

Objective To predict monthly incidents of extended spectrum β-Lactamases (ESBLs)-producing Escherichia coli in Zhejiang Hospital by establishing multiple seasonal autoregressive integrated moving average (ARIMA) model, so as to provide scientific evidence for reducing the incidents of nosocomial infection of ESBLs producing Escherichia coli. Methods Multiple seasonal ARIMA model was established by monthly records of ESBLs producing Escherichia coli from 2010 to 2016 in Zhejiang hospital. Monthly incidents of ESBLs producing Escherichia coli from 2017 to February 2018 were used to verify the predicted result. The predictions were evaluated by models of mean absolute percent error (MAPE) and bayesian information criterion (BIC) . Results The optional model for the monthly incidence from 2010 to 2016 was ARIMA (0, 1, 1) (0, 1, 1)12. The MAPE was 14.76, BIC was 2.01, and the Ljung-Box statistics value Q was 16.79 (P=0.40) . These parameters suggested a good model fitting. The average relative error between the predictive value and the actual value of the monthly incidents ESBLs producing Escherichia coli from 2017 to February 2018 was 14.08%.The actual values were within the 95% confidence interval. Conclusion The multiple seasonal ARIMA model of ARIMA (0, 1, 1) (0, 1, 1 )12 fits and can be used for short-term prediction and dynamic analysis of the incidents of ESBLs producing Escherichia coli in Zhejiang Hospital.

Impact of carbon dioxide pneumoperitoneum in operating rooms on the health of medical staffs / 中华劳动卫生职业病杂志

Objective@#To evaluate the impact of CO2 pneumoperitoneum in operating rooms on the health of medical staffs.@*Methods@#In June 2016, the thirty-three medical staffs in operating rooms were chosen as the object of the research.Seventeen people who took part in the pneumoperitoneum operation were selected as a exposure group and sixteen people who took part in the laparotomy operation were selected as a control group.Vital signs and arterial blood gases of medical staffs in the two groups were both measured in pre-operation and post-operation. Occupational Health Questionnaires were conducted to collect information on age, weight and postoperative symptoms. The level of CO2 in operating room was determined by a portable infrared CO2 analyzer.@*Results@#Compared with the control group, the concentration of CO2 in the exposed group was higherat T1, T2 and T3 (t=22.227, 13.583, 17.408, P<0.05) . Heart rates and PaCO2 in the exposure group raised greatly (t=2.132, 2.129, P<0.05) , while pH decreased (t=-3.015, P<0.05) . The differences between the two groups were statistically significant.@*Conclusion@#The increase of mild acidosis and thesense of job burnout in medical staffs could be caused by CO2 pollution in the operating rooms.

[A survey on adolescent scoliosis in Guangzhou].

OBJECTIVE: To investigate the prevalence of adolescent scoliosis in Guangzhou for development of effective prevention and treatment program to the disease. METHODS: From November 2007 to July 2009, 30 142 students between 7 to 20 years old in primary and junior middle schools received physical check-up for detection of scoliosis through physical and radiographic examination. RESULTS: 211 cases were diagnosed as scoliosis (Cobb angle ≥ 10°), with the prevalence rate as 0.70%. 192 patients with idiopathic scoliosis (IS) were detected, accounting for 91.00%. There were 19 cases of congenital scoliosis, accounting for 9.00%. Sex ratio of scoliosis was 180/31. The prevalence of scoliosis was significantly lower in boys than that in girls (χ(2) = 112.332, P < 0.001). CONCLUSION: The crude prevalence of adolescent scoliosis was 0.70% in Guangzhou with majority of idiopathic scoliosis. Investigation on scoliosis among school-age population seemed to be important for the purposes of early diagnosis, selection of effective prevention and treatment.

A survey on adolescent scoliosis in Guangzhou / 中华流行病学杂志

Objective To investigate the prevalence of adolescent scoliosis in Guangzhou for development of effective prevention and treatment program to the disease. Methods From November2007 to July 2009, 30 142 students between 7 to 20 years old in primary and junior middle schools received physical check-up for detection of scoliosis through physical and radiographic examination.Results 211 cases were diagnosed as scoliosis (Cobb angle≥10°) , with the prevalence rate as 0.70%. 192 patients with idiopathic scoliosis (IS) were detected, accounting for 91.00%. There were 19 cases of congenital scoliosis, accounting for 9.00%. Sex ratio of scoliosis was 180/31. The prevalence of scoliosis was significantly lower in boys than that in girls (x2= 112.332, P＜0.001 ).Conclusion The crude prevalence of adolescent scoliosis was 0.70% in Guangzhou with majority of idiopathic scoliosis. Investigation on scoliosis among school-age population seemed to be important for the purposes of early diagnosis, selection of effective prevention and treatment.