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OBJECTIVE:To investigate the effects of UGT1A4142T>G polymorphism and blood concentration of valproic ac-id(VPA)on blood concentration of lamotrigine(LTG)in southern Chinese Han children with epilepsy,and to establish the predic-tion equation for quantitatively estimating blood concentration of LTG. METHODS:A total of 72 southern Chinese Han children with epilepsy selected from Guangzhou Women and Children's Medical Center during Jan. 2010-Sept. 2016 were given LTG+VPA. LC-MS/MS and enzyme amplified immunoassay were adopted to determine the blood concentration of LTG and VPA. RFLP-PCR was adopted to determine UGT1A4142T>G polymorphism. The relationships of age, gender, blood concentration of VPA, UGT1A4142T>G polymorphism and LTG concentration-to-dose-ratio (CDR) were also investigate. The prediction equation for blood concentration of LTG was established by multiple linear regression analysis. RESULTS:Age and blood concentration of VPA were positively related to CDR of LTG(r=0.225,0.300,P0.05). UGT1A4 TT,TG and GG genotypes were detected in 39,29,and 4 cases respectively;the frequencies of each genotype were in line with the Har-dy-Weinberg balance(P>0.05). CDR of LTG of TT genotype was significantly lower than those of TG and GG genotype,with sta-tistical significance(PG polymorphism(x4)were all related to blood concentration of LTG(PG polymorphism may associated with blood concentration of LTG. Established prediction equation can provide reference for precise medication in south-ern Chinese Han children with epilepsy.
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OBJECTIVE:To investigate off-label drug use of Ambroxol hydrochloride injection,and to provide reference for further evidence-based evaluation on rationality and standardized management of off-label drug use. METHODS:All medical orders for inpatients receiving Ambroxol hydrochloride injection were selected from 10 hospitals of Guangdong province during Apr. 2014 to Mar. 2015. Situation of drug use in different categories of departments was summarized,the incidence of off-label administation route and off-label dosage were analyzed;according to drug package inserts,prescription daily dose(PDD)and drug utilization in-dex(DUI)were calculated for each category of department,and the degree of off-label dosage was evaluated. RESULTS:A total of 761 821 person·day who used Ambroxol hydrochloride injection was included. Off-label drug use occurred in each category of departments,and the incidence of off-label drug use was 62.10%. The incidence of off-label administration route was 40.51%, mainly atomization inhalation;the incidence of it was the high-est in gynecology and obstetrics department(92.70%).The in-cidence of off-label dosage was 36.30%,and the incidence of it was the highest in cardiothoracic surgery department (85.36%). Departments whose PDDs were higher than the drug package inserts were cardiothoracic surgery department,ICU,surgical department,cardiovascular medicine department,emer-gency department,department of internal medicine and pediatrics department.CONCLUSIONS:Off-label drug use of Ambroxol hy-drochloride injection is common,and the effectiveness,safety and necessity remain controversial,which need to be proved by multi-center randomized controlled prospective trial.
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Objective To investigate the effect of age,gender,weight and UGT1A4142T>G gene poly-morphism on the efficacy of LTG in epileptic children treated with valproic acid ,and to determine the effective se-rum concentration of LTG in children with epilepsy in south China. Methods A total of 72 pediatric patients with epilepsy received LTG and VPA treatments were enrolled in this study. Patients were treated from January 2010 to September 2016 in Guangzhou women and childrens′medical center. Serum concentration of LTG was measured by using the liquid chromatography-tandem mass spectrometry. UGT1A4142T > G was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The correlations between the efficacy of LTG and age,gender,weight were analyzed by chi-square test,non-parametric test and logistic regression analysis,respec-tively. Results The curative effect of patients who were younger and with lighter weight were relatively poor ,and men were better than women in the curative effect. UGT1A4142T > G was not related with LTG efficacy. When combined with VPA,the effective serum concentration of LTG in children with epilepsy was more than 2 g/mL. Conclusion There is a good correlation between age and LTG curative effect. The effective serum concentration of LTG in children with epilepsy,who were co-treated with VPA,was more than 2 g/mL. This study provides a refer-ence for the individual administration of children with epilepsy in south China.
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OBJECTIVE:To investigate off-label drug use of Ambroxol hydrochloride injection,and to provide reference for further evidence-based evaluation on rationality and standardized management of off-label drug use. METHODS:All medical orders for inpatients receiving Ambroxol hydrochloride injection were selected from 10 hospitals of Guangdong province during Apr. 2014 to Mar. 2015. Situation of drug use in different categories of departments was summarized,the incidence of off-label administation route and off-label dosage were analyzed;according to drug package inserts,prescription daily dose(PDD)and drug utilization in-dex(DUI)were calculated for each category of department,and the degree of off-label dosage was evaluated. RESULTS:A total of 761 821 person·day who used Ambroxol hydrochloride injection was included. Off-label drug use occurred in each category of departments,and the incidence of off-label drug use was 62.10%. The incidence of off-label administration route was 40.51%, mainly atomization inhalation;the incidence of it was the high-est in gynecology and obstetrics department(92.70%).The in-cidence of off-label dosage was 36.30%,and the incidence of it was the highest in cardiothoracic surgery department (85.36%). Departments whose PDDs were higher than the drug package inserts were cardiothoracic surgery department,ICU,surgical department,cardiovascular medicine department,emer-gency department,department of internal medicine and pediatrics department.CONCLUSIONS:Off-label drug use of Ambroxol hy-drochloride injection is common,and the effectiveness,safety and necessity remain controversial,which need to be proved by multi-center randomized controlled prospective trial.
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Objective To investigate the effect of age,gender,weight and UGT1A4142T>G gene poly-morphism on the efficacy of LTG in epileptic children treated with valproic acid ,and to determine the effective se-rum concentration of LTG in children with epilepsy in south China. Methods A total of 72 pediatric patients with epilepsy received LTG and VPA treatments were enrolled in this study. Patients were treated from January 2010 to September 2016 in Guangzhou women and childrens′medical center. Serum concentration of LTG was measured by using the liquid chromatography-tandem mass spectrometry. UGT1A4142T > G was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The correlations between the efficacy of LTG and age,gender,weight were analyzed by chi-square test,non-parametric test and logistic regression analysis,respec-tively. Results The curative effect of patients who were younger and with lighter weight were relatively poor ,and men were better than women in the curative effect. UGT1A4142T > G was not related with LTG efficacy. When combined with VPA,the effective serum concentration of LTG in children with epilepsy was more than 2 g/mL. Conclusion There is a good correlation between age and LTG curative effect. The effective serum concentration of LTG in children with epilepsy,who were co-treated with VPA,was more than 2 g/mL. This study provides a refer-ence for the individual administration of children with epilepsy in south China.
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OBJECTIVE:To set up a LC-MS/MS method for determination of plasma concentration of methadone.METHODS:Methadone was extracted with ethyl acetate and dichloromethane(4∶1)and the residues were analyzed with a LC-MS/MS system using Agilent TC C18 column at a column temperature of 25 ℃ with the mobile phase consisted of methanol-5 mmol?L-1 ammonium formate(90∶10)at a flow rate of 1 mL?min-1.An agilent 6410 triple quad mass spectrometer system equipped with an electrospray ionization ion-trap source was used as the detector and operated in the positive ion mode.Selected reaction monitoring(SRM)using the precursor to product ion combinations of m/z 310.0→264.9 and m/z 285.1→154.0 was performed to detect methadone and diazepam(the internal standard),respectively.RESULTS:The calibration curves for methadone had good linearity over the range of 2.5～500 ?g?L-1(r=0.999 0).The limits of quantitation for methadone was 2.5 ?g?L-1.The average recoveries for methadone(at high,medium and low concentrations)were 100.23%,101.20% and 101.39%,respectively.The within-day RSD(n=5)and between-day RSD(n=3)were all less than 10%.CONCLUSION:The method is simple,rapid,sensitive,accurate,and reproducible and it provides an analytical procedure for clinical monitoring of plasma concentration of methadone and its pharmacokinetic studies.
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OBJECTIVE: To prepare Yizhi Mixture and establish a method for its quality control. METHODS: The mixture was prepared by water decoction method,Radix Polygalae,Cortex Phellodendri,and Radix et Rhizoma Glycyrrhizae uralensis Fisch.in the mixture were identified qualitatively by TLC. The contents of trace amount of paeoniflorin in Yizhi mixture was determined by HPLC. RESULTS: The studies on the quality control showed that the characteristics for identification by TLC were distinct. The linear range of peoniflorin was 0.25～10 mg?L-1.The average recovery was 99.06% and its RSD was 4.91%(n=5).CONCLUSION: The mixture is reasonable in formula and simple in preparation technology. A quality standard has been established for the mixture. The methods for identification and quantification were simple, reliable and practical.
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OBJECTIVE:To establish a HPLC method for the determination of cilostazol in human plasma.METHODS:C18 was the chromatographic column,MeOH-0.03mol/L ammonium acetate (62∶38,V/V)was the mobile phase with a flow rate at 0.8 ml/min and detection wavelength at 257 nm,acetic ether was used as the extraction solvent.RESULTS:Good linear relationship was achieved when the detection concentration range of cilostazol was 10.0～1 500.0 ng/ml(r=0.9 999),the average recovery rates for the high,medium and low concentrations of cilostazol were 99.82%,97.30%and 97.14%,respectively,both the intra-day and inter-day RSD were lower than 6%.CONCLUSION:This method is sensitive,accurate,simple and fast,which can be used as the clinical monitoring of blood concentration of cilostazol and its pharmacokinetics study.
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OBJECTIVE:To study the pharmacokinetics of escitalopram oxalate tablets in human body.METHODS:Es-citalopram oxalate tablets were administered orally at a single dose of30mg to10healthy subjects respectively,the plasma concentration of escitalopram oxalate was determined by HPLC method,the pharmacokinetic parameter was fitted with3p97software.RESULTS:The concentration-time curve of escitalopram oxalate tablets was in line with the two-compartment model,the main pharmacokinetics parameters of escitalopram oxalate were as follows,the C max was(42.73?10.19)?g?L,t max was(2.90?0.32)h,t 1/2 was(35.34?7.78)h,AUC 0～132 was(1241.5?194.3)(?g?h)/L and the AUC 0～∞ was(1327.5?210.5)(?g?h)/L.CONCLUSION:The study on pharmacokinetics can be used as a reference in the clinical medication.
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OBJECTIVE:To develop HPLC method for quantitative determination of ti anepine sodium in blood plasma METHODS:Tianepine was extracted with ethyl acet ate The residues were analyzed with a reverse phase HPLC system(DiamonsilTM C18 column,4 6mm?250mm,5?m);Mobile phase,MeOH-C2H3OONH4(80∶20);UV detecti on 220nm RESUL_TS:The average recoveries for tianepine sodium in high,medium and low concentr ations were 97 63%,97 60% and 93 67%,respectively The within-day and b etween-day relative standard deviations were less than 5%(n=5) The calibratio n curves had good linearity within a concentration range of 1 0～83 3?g/ml T he regression equation was Y=6 05?10-2X+8 18?10-1,r=0 9 994(n=12) The limit of quantitation for tianepine sodium was 0 2?g/ml CONCLUSION:The metho d provides a se_nsitive,accurate,precise and reliable analytical procedure for clinical monito ring of tianepine sodium blood in plasma and its pharmacokinetic studies
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OBJECTIVE:To develop the method for the determination of riluzole concentration in blood plasma.METH?ODS:Riluzole was extracted with diethyl ether.The residues were analyzed with a reverse phase HPLC system(Diamonsil TM C 18 column,250mm?4.6mm,5?m),with mobile phase of MeOH-0.03mol/L and NH 4 H 2 PO 4 (80∶20,V/V),UV detection wave length of265nm,flow rate of0.8ml/min.RESULTS:The linear coverage of Riluzole was5～1000ng/ml;the lowest detectable concentration was5ng/ml.The average recoveries of riluzole were99.51%,95.74%and97.12respectively.The within-day and between-day relative standard deviations were1.17%、6.48%(n=5)respectively.CONCLUSION:The met_ hod is sensitive,accurate,simple and reliable,and it can be applied to phamacokinetic studies.
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OBJECTIVE:To study the pharmacokinetics of domestic zaleplon tablets in Chinese healthy volun?teers.METHODS:20male healthy subjects received a single oral dose of15mg zaleplon tablets.The plasma concentrations of zaleplon were determined by an improved HPLC method.RESULTS&CONCLUSION:The main pharmacokinetic parameters of zaleplon were as follow:C max was55.90?16.20ng/ml,T max was1.05?0.32h,Ke was0.74?0.18h -1 ,T 1/2Ke was1.00?0.29h,AUC 0～8 was123.70?25.64ng?h/ml,AUC 0～∞ was125.20?25.80ng?h/ml.The results are compara?ble to those reported in foreign literature.