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Selective killing effect of oxytetracycline,propafenone and metamizole on A549 or Hela cells

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Chinese Journal of Cancer Research 2013年第6期25卷 662-670页

作者： Jinhui Shao Guihua Feng Department of Histology and Embryology School of MedicineHubei University of Art and Science

Objective： To determine the selective killing effect of oxytetracycline, propafenone and metamizole on A549 or Hela cells. Methods： Proliferation assay, lactate dehydrogenase （LDH） assay, apoptosis detecting, flow cytometry and western blot were performed. Results： It was found that treatment with propafenone at the concentration of 0.014 g/L or higher for 48 h could induce apoptosis in Hela cells greatly, while it was not observed in oxytetracycline and metamizole at the concentration of 0.20 g/L for 48 h. Oxytetracycline, propafenone and metamizole all displayed evident inhibitory effects on the proliferation of A549 cells. The results of LDH assay demonstrated that the drugs at the test range of concentration did not cause necrosis in the cells. propafenone could elevate the protein level of P53 effectively （P〈0.01）. Conclusions： Oxytetracycline, propafenone and metamizol （dipyrone） all displayed evident inhibitory effects on the proliferation of A549 cells. propafenone also displayed evident inhibitory effects on the proliferation of Hela cells.

关键词： Cancer drug oxytetracycline propafenone metamizol

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体内普罗帕酮及其代谢物的GC-MS检验

分析测试学报 2007年第z1期26卷 44-46页

作者：刘俊亭高利娜王妍中国医科大学药学院药物分析教研室辽宁沈阳110001

In this paper,propafenone in judicial anatomy was quantitated and found to be 11.6 μg/mL in blood,17.8 μg/mL in urine,292 μg/g in gastric content and 196 μg/g in liver with GC-MS. Two metabolites from propafenone have been defined.In conclusion,as the dead body himself is a drug abuser and also his blood concentration of propafenone exceed the fatal dose,this case is finally identified to a death cause from the overdose of propanenone abuse.

关键词： propafenone Metabolite GC-MS

Influence of CYP2D610B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects

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Acta Pharmacologica Sinica 2003年第12期 103-106页

作者： CHEN Bing CAI Wei-Min Department of Clinical Pharmacology, Jinling Hospital, Nanjing 210002, China

AIM: To study the relationship between genotype of CYP2D6* 10B and pharmacokinetics of propafenone enantiomers. METHODS: Genotype of 17 healthy Chinese HAN subjects was determined by an allele specific amplification method. The blood samples (0-15 h) of the subjects were taken after oral administration of a single dose (400 mg) of propafenone hydrochloride. Concentrations of propafenone enantiomers in plasma were measured by a reverse-phase HPLC with precolumn derivatization. RESULTS: Seventeen subjects characterized for CYP2D6* 10B genotype included (*1/*1) (n=4), (*1/*10) (n=5) and (*10/*10) (n=8). The metabolic ratios (lg MR) of the three genotypes were-2.68±0.23, -2.2±0.7, and -1.1±0.5, respectively. The AUC of the three groups were (1534±334), (1891±793), (3171±1075) μg·h·L-1for S-enantiomer and (1136±345), (1467±817), (2277±745) μg·h·L-1for R-enantiomer, respectively. The AUC of propafenone enantiomers in *10/*10 is about 1.5-2 times of that of *1/*10 group or *1/*1 group, a

关键词： propafenone pharmacokinetics CYP2D6~* 10B genotype phenotype enantiomers

Study on the pharmacokinetic interaction of DDPH and propafenone in rats and its mechanism

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Study on the pharmacokinetic interaction of DDPH and propafe...

Enantioselective assay of S(+)- and R(-)-propafenone in human urine by using RP-HPLC with pre-column chiral derivatization

中国药理学会第十次全国学术会议

作者： Xin-Xia Liu,Jiong Hu,Ping Ren,Chang-Rong Guan,Shi-Fen Gu,Hui Chen (Department of Pharmacology,Tongji Medical College,HUST,Wuhan 430030,P.R.China)

Objective To study the pharmacokinetic interaction after oral administration of DDPH and propafenone in rats,and explore the effects of DDPH on the catalytic activities and the expression of CYP2D1,CYP3A1 at protein and mRNA levels.Methods(1) low and high dose of DDPH(12.5,50 mg/kg/d,bid) were administrated to male Sprague-Dawley rats through oral garage for 7 days.On the 8th day,propafenone was administrated to rats at the single dose of 45mg/kg,and the drug concentration was determined by RP-HPLC-UV;(2) low,and high dose of DDPH(12.5,50 mg/kg/d,bid) were administrated to male Sprague-Dawley rats through oral gavage for 7 consecutive days.The rats were sacrificed about 24 h later after the last dose.Livers were harvested and microsomes were prepared aimed at analysis of the activities of.CYP2D1 and CYP3A1,the major cytochrome P4.50 isoforms implicated in the metabolism of propafenone.The expression levels of protein of CYP2D1 and CYP3A1 were assessed by western blot analysis.Total RNA was also isolated and the mRNA levels of CYP2D1 and CYP3A1 were determined by real-time quantitative RT-PCR.Results(1) The co-administration of DDPH significantly affects the pharmacokinetics of propafenone in rats,increasing the AUC(0-8h) and Cmax and reducing the clearance rate. (2) DDPH remarkably inhibited the catalytic activities of CYP2D1 and CYP3A1,in addition,it negatively adjusted the levels of their protein expression and mRNA transcription.Conclusion There was obvious interaction of pharmacokinetics when DDPH and propafenone were co-administered,its mechanism may he related with the decreases of CYP2D1 and CYP3A1 catalytic activities through the regulation at transcriptional level by DDPH.

关键词： DDPH propafenone drug interaction liver microsomes

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2004年第2期5卷 98-101页

作者：吴永江马明铭曾苏 Hangzhou 310031 China Zhejiang University College of Pharmaceutical Sciences

The enantioselective assay for S(+)- and R(-)-propafenone (PPF) in human urine that developed in this work involves extraction of propafenone from human urine and using S(+)-propafenone as internal standard, chiral derivatization with 2,3,4,6-tetra-O-b-D-glucopranosyl isothiocyanate, and quantitation by an RP-HPLC system with UV detection (l=220 nm). A baseline separation of propafenone enantiomers was achieved on a 5-mm reverse phase ODS column, with a mixture of methanol:water:glacial acetic acid (25:12:0.02,v/v) as mobile phase. There was good linear relationship from 24.9 ng/ml to 1875.0 ng/ml for both of enantiomers. The regression equations of the standard curves based on CS-PPF (or CR-PPF ) versus ratio of AS-PPF/AS (or AR-PPF/AS ) were y=0.0032x-0.081, (r=0.999) for S-PPF and y=0.0033x+0.0039, (r=0.998) for R-PPF, respectively. The method抯 limit of detection was 12.5 ng/ml for both enantiomers, and the method抯 limit of quantitation was 28.20.52 ng/ml for S-PPF, 30.40.53 ng/ml for R-PPF (RSDpropafenone in human urine. The results from 7 volunteers administered 150 mg racemic propafenone indicated that propafenone enantiomers undergo stereoselective metabolism and that in the human body, S(+)-propafenone is metabolized more extensively than R(-)- propafenone.

关键词： Enantioselective assay propafenone Human urine Chiral derivatization High-performance liquid chroma-tography

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心律平治疗小儿心律失常30例临床观察

西安交通大学学报(医学版) 1987年第4期 391-393页

作者：曹容珍苏祖佑陈顺昌杨素云赵春平西安医科大学第一附属医院儿科学教研室西安医科大学第一附属医院儿科学教研室进修医师

心律平是一种高效、速效、安全的抗心律失常药。我们应用此药口服治疗30例心律紊乱惠儿。首次剂量为5～8mg/kg,长期服药为20～25mg/kg/日,分4次、每6小时一次。服药后半小时～3小时,出现效果。30例均有显效(90％)。本药对传导系统有轻... 详细信息

心律平是一种高效、速效、安全的抗心律失常药。我们应用此药口服治疗30例心律紊乱惠儿。首次剂量为5～8mg/kg,长期服药为20～25mg/kg/日,分4次、每6小时一次。服药后半小时～3小时,出现效果。30例均有显效(90％)。本药对传导系统有轻度抑制作用。

关键词： arrhythmia propafenone

Electrophysiologic Effects of propafenone on Action Potential of Neonatal and Adult Purkinje Fibers

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中国医科大学学报 1991年第S2期20卷 37-42页

作者：徐惠郝丽英张克仪 Arthur S.Pickoff Adrienne Stolfi Dept of Pediatrics The First Affiliated Hospital China Medical University Shenyang China Department of Pediatrics Tulane University Medical Center USA M.D. Department of Pediatrics Tulane University Medical Center USA

The electrophysiological effects of 5.8×10-6 mol/L propafenonewere studied in neonatal canine Purkinje fiber compared with changes in theadult canine. The method used was microelectrode technique. This study sug-gests that Purkinje fibers are less sensitive to propafenone in the neonate than inthe adult, but at shorter ample lengths, the difference between them is not sig-nificant.

关键词： propafenone action potential Purkinje fibers

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propafenone对心律失常的疗效

中国药理学通报 1991年第1期 4-4页

作者：朱兆华

propafenone是IC类抗心律失常药,在欧洲治疗各类心律失常已有10余年的历史。最近美国己用于治疗危及生命的定性心律失常,例如持续性室性心动过速,作为口服药销售。钠通道阻滞剂propafenone的结构式不仅与IC类抗心律失常药相似,而且也与... 详细信息

propafenone是IC类抗心律失常药,在欧洲治疗各类心律失常已有10余年的历史。最近美国己用于治疗危及生命的定性心律失常,例如持续性室性心动过速,作为口服药销售。钠通道阻滞剂propafenone的结构式不仅与IC类抗心律失常药相似,而且也与心得安有联系。对于正常心律,该药能延长PR和QRS间期,属典型的IC类抗

关键词：心律失常生命 IC propafenone 疗效

普罗帕酮(propafenone)治疗WPW综合征的效果:电生理测试结果和长期随访

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国外医学.心血管疾病分册 1988年第1期 57-58页

作者：孙仰龙

一、普罗帕酮静脉注射的即时效果。12～58岁的12(男7、女5)例典型的WPW综合征(10例)和隐匿性附加通道(2例)患者参加了随机、双盲、安慰剂对照的条件交叉试验,各例均有晕厥史和/或室上性心律失常反复发作史且经常规抗心律失常药物治疗无... 详细信息

一、普罗帕酮静脉注射的即时效果。12～58岁的12(男7、女5)例典型的WPW综合征(10例)和隐匿性附加通道(2例)患者参加了随机、双盲、安慰剂对照的条件交叉试验,各例均有晕厥史和/或室上性心律失常反复发作史且经常规抗心律失常药物治疗无效。试验前至少停用心脏活性药物5个半衰期,仅1例继续服用胺碘达隆(200mg/d)者例外。插管开始电生理测试,首先诱发持续性室上(性心动过)速,然后(在10分钟内)静脉注入普罗帕酮2mg/kg(或安慰剂),若无效改用程序电刺激终止

关键词：普罗帕酮 propafenone WPW 综合征综合病症电生理