1.Effects of CYP2C19 polymorphism on pharmacokinetic profile and comparative bioavailability of omeprazole
Jingjing MA ; Jinheng LI ; Xiaomei CAO ; Zunjian ZHANG ; Yuan TIAN
Chinese Pharmacological Bulletin 2010;26(2):258-262
Aim To investigate the effects of CYP2C19 polymorphism on the pharmacokinetics and comparative bioavailability of omeprazole in Chinese population.Methods Eighteen healthy male volunteers were selected,of whom 6 were CYP2C19 wild type(w/w),6 were CYP2C19 heterozygous variant(w/m) and the rest were CYP2C19 homozygous variant(m/m).A randomized two-period crossover study was performed.Subjects were assigned to receive test or reference omeprazole as a single oral dose of 40 mg randomly.After a washout period of one week,subjects received the alternative omeprazole formulation.Multiple blood samples of 3 ml were obtained over 12 h after dosing and plasma concentrations of omeprazole were measured by LC/MS method.The modeling of individual pharmacokinetics and the pharmacokinetic parameters of omeprazole were estimated by 3P97.Results The AUC and Cmax of reference omeprazole formulation in w/w,w/m,m/m groups were 1178.44±340.24,2328.10±1011.83,5062.02±1097.29 μg·h·L~(-1) and 602.87±118.25,926.43±134.48,1406.29±233.58 μg·L~(-1),respectively,with significant differences among the three groups(P<0.05).Significant differences were also observed in other pharmacokinetic parameters such as k_e、CL/F、t_(1/2) and Vd/F among the three groups(P<0.05).With regard to test omeprazole formulation,the AUC and C_(max) in w/w,w/m,m/m groups were 1224.82±531.67,2723.34±519.29,5692.49±1575.35 μg·h·L~(-1) and 618.74±231.43,910.67±125.99,1303.31±152.01 μg·L~(-1),respectively,which,as well as k_e,CL/F,t_(1/2) and Vd/F were significant different among the three groups(P<0.05).No significant differences were observed in comparative bioavailability among groups with the values of 94.29%±14.06%,93.08%±11.22%,91.84%±13.03% in w/w,w/m,m/m groups respectively(P>0.05).Conclusions Different CYP2C19 genotypes,leading to functional heterogeneity of CYP2C19,may affect pharmacokinetic profile of omeprazole.Therefore,genotyping CYP2C19 gene before omeprazole therapy will be of great benefit for optimizing individual therapy regimen.There is no significant difference of omeprazole comparative bioavailability with regard to CYP2C19 genetic polymorphism.
3.Physiological pharmacokinetic model of children and its application of modeling software
Xu ZHOU ; Yuan-yuan WEI ; Tao MA ; Yue-zhou TANG ; Yun-jie DANG ; De-ying CAO
Acta Pharmaceutica Sinica 2023;58(2):320-329
Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.
4.Effect of different-dose atorvastatins on serum High sensitive C-reactive protein、Interleukin-10 and Monncyte chemoattractant protein-1 levels in post-intervention patients with coronary stenting
Jiangwei MA ; Zengyong QIAO ; Li ZHANG ; Hua CAO ; Yuan TAO ; Huajin LIU ; Dinhong JIN ; Cuiqing ZHU
Chinese Journal of Primary Medicine and Pharmacy 2010;17(16):2176-2178
Objective To Discuss the impacts of different dosage of atorvastatirs on serum hsCRP,IL-10 and MCP-1 levels on post-intervention patients with coronary stenting. Methods 93 post-intervention patients with coronary stenting were selected and randomly divided into 3 groups.Each group took different dosage of oral atorvastatins after the operation for more than one week.The dosage for each group was 10 mg,20 mg and 40 mg,respectively.Each patient was phlebotomized for three times,which are 24 hours before the operation,24 hours after the operation and one week after the operation.Serum MCP-1,IL-10 and hs-CRP levels were measured by enzyme linked immunosorbent assay(ELISA)and immunoturbidimetry(ITM). Results Serum hs-CRP and MCP-1 levels of post-intervention patients were significantly higher than those of pre-intervention.This illustrated that the serum hsCRP and MCP-1 levels were closely related to PCI.Serum hs-CRP and MCP-1 levels decreased in those patients one week after operation which proves they are negatively correlated with the dosage of atorvastatins.There was no statistic evidence to prove the correlation between different dosage of atorvastatins and the level of serum IL-10.The ratio of MCP-1/IL-10 at 24h post-intervention patient was significantly higher than pre-intervention,which proves the ratio was negatively correlated with the dosage of atorvastatins. Conclusion Atorvastatins decreases serum MCP-1 and hs-CRP levels after PCI.Serum MCP-1 and hs-CRP levels were negatively correlated with the dosage of atorvastatins.
5.Effect of acitretin on the T helper cells of psoriasis vulgaris
Wei CAO ; Xinwu NIU ; Jie FENG ; Jianyu HE ; Chen HUANG ; Huiqun MA ; Jingyi YUAN
Journal of Pharmaceutical Analysis 2010;22(3):198-202
Objective To investigate the effects of acitretin on T helper cell (Th) 1/Th2 balance and Th17 cells in psoriasis vulgaris (PV) patients. Methods A total of 13 men and 17 women with PV were investigated. 10 mg of acitretin was administered twice a day for 8 weeks for intervention therapy. Serum levels of interferon-gamma (IFN-γ), interleukin (IL)-4 and IL-17 were measured by enzyme-linked immunosorbent assay. T, Th1, Th2 and Th17 cells in skin biopsies were counted with double-labeled immunofluorescence. Psoriasis Area and Severity Index (PASI) score was calculated before and 8 weeks after treatment. Results Before treatment PV patients had higher serum levels of IFN-γ and IL-17, and increased T, Th1 and Th17 cells in skin biopsies. After treatment, both serum levels of IFN-γ and IL-17, and T, Th1 and Th17 cells infiltrating in PV skin decreased significantly. Th1/Th2 balance was restored to normal. However, their IL-4 and Th2 cells showed no significant change throughout the therapy. Conclusion Acitretin exerts influence on dermal Th1/Th2 balance and Th17 cell infiltration, so does it on production of systematic inflammatory cytokines IFN-γ and IL-17 in PV patients. However, Th2 cells and its derivative cytokine-IL-4 are not affected.
6.Incidence analysis of malignant cancer in Shanxi cancer registration areas in 2011
Yongzhen ZHANG ; Ling CAO ; Zhaohui MA ; Fang SU ; Yi XU ; Yuan WANG ; Ruifeng ZHANG ; Xinchen WANG
Cancer Research and Clinic 2016;28(7):471-475
Objective To explore the cancer incidence in registration areas in Shanxi Province. Methods Data of 8 cancer registration areas in 2011 were taken into account and cancer incidence in different areas with different ages was compared with that in other domestic areas. Results 8 395 new cases in Shanxi all cancer sites were reported in 2011, including 4 810 male and 3 585 female. The incidence of malignant cancer of Shanxi was 207.53/100 000, and the standardized incidence of Chinese population and world population were 125.20/100 000 and 165.72/100 000, respectively. In urban areas, the incidence of Shanxi and the standardized incidence of Chinese population were 202.49/100 000 and 112.81/100 000, respectively. In rural areas, incidence rate of Shanxi was 211.96/100 000 and the standardized incidence of Chinese population was 138.43/100 000. In Shanxi Province, the major malignant cancer sites for males involved stomach, lung, esophagus, liver and colorectum, and cancer sites for females were more on cervix, lung, breast, stomach and esophagus. Conclusions Upper gastrointestinal cancer and uterine cervix cancer are the major cancers in Shanxi registration areas. The incidence of stomach cancer and uterine cervix cancer in Shanxi Province are much higher than national average.
7.Effect of partial foraminotomy after laminoplasty surgery on preventing C5 nerve root palsy
Wei HU ; Xinlong MA ; Sheng CAO ; Jianjun YUAN ; Liming TIAN ; Xueli ZHANG
Chinese Journal of Orthopaedics 2015;35(6):617-623
Objective To investigate clinical curative effect of partial foraminotomy after C4.5 ossification of posterior longitudinal ligament (OPLL) on preventing C5 nerve root palsy.Methods A total of 155 patients with OPLL were treated with expansion open-door laminoplasty (EOLP) between January 2008 and October 2012,including 75 male patients and 80 female patients,with average age of 54.5 (ranging from 38 to 75).Among them,90 cases took EOLP (open team),and 65 cases took EOLP and C4.5 partial foraminotomy (incision team).Clinical curative effect and imaging evaluation were used in 8 weeks and 12 months after operation.JOA scores,JOA scores improvement rate,C5 nerve root palsy occurrence rate,neurological function of patients with C5 nerve root palsy and the prognosis,cervical curvature index,opening angular variation,backward drift distance of anterior margin and posterior margin of the spinal cord were evaluated after 8 weeks and 1 year after the surgery.Results The operation time was 90-140 min,with the average time of 110±14 min;mean bleeding volume was 160±45 ml (ranging from 100 to 250 ml);follow-up visit time was 15.4 months on average (ranging from 12 to 18 months).JOA score and improvement rate after 8 weeks and 1 year of the operation have no statistical significance.The C5 nerve root palsy occurrence rate in open team was 8.89% (8/90),while that in incision team was 4.62% (3/65).The difference of two groups has statistical significance.C5 nerve root palsy all happened in laminar opening side.Comparison of cervical curvature index of two groups before the operation and after 8 weeks of the operation and inter-group comparison have no statistical significance.The difference between laminar opening angle after 1 year of the operation and laminar opening angle after 8 weeks has no statistical significance.The difference of backward drift distance of anterior margin of the spinal cord at different time after the operation and inter-group difference have no statistical significance.The difference in backward drift distance of posterior margin of the spinal cord between 1 year after the operation and 8 weeks after the operation has no statistical significance.Conclusion Treating OPLL with EOLP and C4.5 partial foraminotomy can reduce occurrence rate of C5 nerve root palsy,but has no significant influence on JOA score improvement rate.
8.Evaluation of Patients with Obstruction of Biliary Tract by Multi-Detector Row CT Using Reconstruction Techniques
Zenglin MA ; Liying HE ; Yuchang YAN ; Bin ZHANG ; Xiuhua LU ; Wenjie YUAN ; Baoxin CAO
Chinese Journal of Medical Imaging 2009;(6):431-435
Purpose:To evaluate the role of multi - detector row CT(MDCT) using reconstruction techniques in the assessment of patients with obstructed diseases of biliary tract.Materials and Methods: 47 Patients with obstructed diseases of biliary tract confirmed clinically underwent MDCT and their reconstructed images of biliary tract including multi-planar reconstruction (MPR) images and curved planar reconstruction(CPR) images were compared with those of 50 patients without obstruction and dilatation of biliary tract.The display effect of biliary duct structure and biliary duct wall and the display ability of biliary tract by MPR and CPR images between the 2 groups were compared and analysed.The reconstruction images of biliary tract were analysed retrospectively to evaluate the location and possible causes of biliary obstruction.Results: The display effect of biliary duct structure and biliary duct wall in MPR and CPR images of the group with biliary obstruction is better than that of control group,and the display ability of biliary tract in CPR images of the group with biliary obstruction is also better than that of control group.The accuracy of localization and cause evaluation of obstruction by MPR and CPR images is 100% and 89.4% respectively.Conclusions: The MPR and CPR images of MDCT provide a good display of biliary duct structure,biliary duct wall and an accurate evaluation of obstruction localization.The reconstruction technique of MDCT such as MPR and CPR should be widely applied in the evaluation of biliary obstruction.
9.Clinical treatment of double or above disruptions of the superior shoulder suspensory complex
Jinli ZHANG ; Qing CAO ; Tianxiang YUAN ; Jianhua YANG ; Qiang DONG ; Baotong MA
Chinese Journal of Orthopaedics 2011;31(7):729-733
Objective To summarize the classification and surgical treatment of double or above disruptions of the superior shoulder suspensory complex(SSSC)retrospectively.Methods From June 2006to March 2010,26 consecutive patients with double or above disruptions of the SSSC were treated and entered in the study,including 18 males and 8 females with an average age of 42 years(range,16-80).All patients received surgical treatment,these included clavicle fracture and scapular neck fracture in 9 cases (type Ⅰ),distal clavicle fracture or dislocation and coracoclavicular ligament and acromioclavicular joint injury in 10(type Ⅱ),distal clavicle fracture and other injuries in the SSSC in 7(type Ⅲ).The duration from injury to surgery was 6.4 days(range,3-10).Scapular neck fracture and scapular area dishes fracture were fixed with reconstructive plate and canulated screws,acromial fracture was treated with reconstructive plate and canulated screws,clavicle fracture was fixed with reconstructive plate or hook plate,coracoid fracture was fixed with canulated screw.All patients were treated with primary repair for ligament injuries.The surgery effect was assessed with Rowe and Constan-Murley systems after the fractures reunion.Results All patients were successfully followed up,and the average time was 18.7 months(range,12-32).Fractures were healed with an average of 8.2 weeks(range,6-12 weeks).There was no inferior shoulder knocking syndrome after surgery.Patients all felt shoulder in a stable status.Two patients appeared deltoid muscle power decline,3 appeared shoulder fatigue and aching pain.The average score was 89.7(range,71-97)according to the Rowe system.Eighteen cases were grade as excellent,5 as good,and 3 as fair.The average score was 92.4(range,70-100)according to the Constant-Murley system.Sixteen cases were grade as excellent,6 as good,and 4 as fair.Conclusion Double or above disruptions of the SSSC can be classified into three types,and surgical treatment with constructive plate and canulated screws for them is a good option.
10.Effect of sub-chronic exposure to deltamethrin on spatial learning and memory in mice
Pei CAO ; Peng GAO ; Ning MA ; Chenxi LI ; Yongquan FENG ; Yuan ZHI ; Haibin XU
Chinese Journal of Behavioral Medicine and Brain Science 2014;23(3):248-250
Objective To study the effect of sub-chronic exposure to dehamethrin(DM) on the behavior of mice in learning and memory.Methods 60 Female SPF Kunming mice were randomly divided into 4 groups and given DM by gavaging for 60 days.Morris water maze (MWM) was used to evaluate spatial memory in mice.Results After exposure to DM,the escape latency of the solvent control group and the treatment groups were (12.20±6.5)s,(14.99±5.4) s,(15.64±8.3)s,(22.71±6.2)s on the fifth day.The escape latency of the high-dose group was higher than those of the low-dose group (P=0.0041) and the solvent control group (P=0.019) in the navigation test.The number of crossing position of the platform in the high-dose group ((2.93± 1.53)times) and the middle-dose group ((3.40± 1.12) times) were lower than that in the solvent control group ((5.87 ± 1.55) times) and the low-dose group ((4.90± 1.41)times)(P<0.05).Conclusion Sub-chronic exposure to DM can damage the spatial learning and memory of mice.