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Comparative pharmacodynamic, pharmacokinetic and tissue distribution of Dahuang-Gancao decoction in normal and experimental constipation mice

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Chinese Journal of Natural Medicines 2019年第11期17卷 871-880页

作者： CHEN Yan-Yan CAO Yu-Jie TANG Yu-Ping YUE Shi-Jun DUAN Jin-Ao Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility and State Key Laboratory of Research&Development of Characteristic Qin Medicine Resources(Cultivation)and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Researchand Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationShaanxi University of Chinese MedicineXi’an 712046China Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicineand Jiangsu Key Laboratory for High Technology Research of TCM FormulaeNanjing University of Chinese MedicineNanjing 210023China

Dahuang-Gancao decoction(DGD)is a classical formula,which is commonly used for reliving constipation in Chinese *** aim of this study was to investigate the pharmacodynamic,pharmacokinetic and tissue distribution alternations of DGD in normal and constipation *** exhibited stronger purgative effect in constipation mice by the increased fecal excretion and reduced first defection time compared with normal *** Cmax,AUC0-t and MRT0-t of rhein,aloe-emodin,rhein-8-O-β-D-glucoside,sennoside A,and glycyrrhizic acid as main bio-active components in DGD were markedly increased in constipation *** tissue distribution of the analytes in constipation mice were higher than those in normal mice with rhein>rhein-8-O-β-D-glucoside>aloe-emodin>glycyrrhizic acid>emodin in liver,and glycyrrhizic acid>rhein-8-O-β-D-glucoside>liquitin>sennoside A>rhein>aloe-emodin>emodin in *** kidney concentrations of the analytes showed a descending order of rhein>rhein-8-O-β-D-glucoside>sennoside A>glycyrrhizic acid>aloe-emodin>emodin,most of them were higher while rhein was lower in constipation mice than normal *** higher exposure of the anthraquinones in plasma,liver and colon may result in the stronger purgative effect in the constipation mice than normal *** is mainly excreted through the kidney,the decreased level of rhein in constipation mice may explain the alleviated side *** of glycyrrhizic acid in colon may related with the moderate property of *** results provided the experimental basis for understanding the therapeutic effects and metabolite profile of DGD.

关键词： Rhubarb Licorice pharmacodynamic Pharmacokinetic Tissue distribution Constipation

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Study on the Intervention Effects of Pinggan Prescription(平肝方) on Spontaneously Hypertensive Rats Based on Metabonomic and pharmacodynamic Methods

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Chinese Journal of Integrative Medicine 2019年第5期25卷 348-353页

作者： XIE Jun JIANG Hai-qiang LI Yun-lun NIE Lei ZHOU Hong-lei YANG Wen-qing Department of Cardiology Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250011)China Medical School Shandong Xiehe UniversityJinan(250109)China Experimental Center Shandong University of Traditional Chinese MedicineJinan(250355)China School of Pharmaceutical Sciences College of PharmacyShandong UniversityJinan(250012)China

Objective: To investigate the effects of Pinggan Prescription(平肝方, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic. Methods: A total of 32 male spontaneously hypertensive rats(SHRs) were randomly divided into two groups by using the random number table method:a treatment group(n=18) and a model group(n=14). The Wistar rats(n=14) were used as the normal *** prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg(PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate(c AMP) and angiotensinⅡ(Ang Ⅱ) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry(GC-MS). Results: Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP(Ppharmacodynamic results illustrated that the content of Ang Ⅱincreased with the raised blood pressure and the c AMP expressed the converse trend. After curing with PGP, the content of Ang Ⅱ decreased, the difference between model group and treatment group was signi?cant(P<0.01),and the c AMP expressed the converse trend. Five potential biomarkers were identi?ed, including arachidonic acid,hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown signi?cantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were signi?cantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with th

关键词： hypertension Pinggan Prescription Chinese medicine metabonomic pharmacodynamic

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Pharmacokinetic and pharmacodynamic responses to cardiovascular drugs in Asians

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Acta Pharmacologica Sinica 1998年第S1期 15-16页

Ｔｈｅｒｅｓｐｏｎｓｅｔｏｄｒｕｇｓｍａｙｖａｒｙｂｅｔｗｅｎｉｎｄｉｖｉｄｕａｌｓｏｒｅｔｈｎｉｃｇｒｏｕｐｓｂｅｃａｕｓｅｏｆｇｅｎｅｔｉｃａｎｄｅｎｖｉｒｏｎｍｅｎｔａｌｆａｃｔｏｒｓ，ｗｈｉｃｈｍａｙｉｎｆｌ... 详细信息

Ｔｈｅｒｅｓｐｏｎｓｅｔｏｄｒｕｇｓｍａｙｖａｒｙｂｅｔｗｅｎｉｎｄｉｖｉｄｕａｌｓｏｒｅｔｈｎｉｃｇｒｏｕｐｓｂｅｃａｕｓｅｏｆｇｅｎｅｔｉｃａｎｄｅｎｖｉｒｏｎｍｅｎｔａｌｆａｃｔｏｒｓ，ｗｈｉｃｈｍａｙｉｎｆｌｕｅｎｃｅｔｈｅｐｈａｒｍａｃｏｋ...

关键词： and pharmacodynamic responses to cardiovascular drugs Asians Pharmacokinetic

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A Pharmacokinetic and pharmacodynamic Study on Intravenous Cefazedone Sodium in Patients with Community-acquired Pneumonia

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Chinese Medical Journal 2015年第9期128卷 1160-1164页

作者： Lei Gao Yan Zhu Yuan Lyu Feng-Lan Hao Pu Zhang Min-Ji Wei Institute of Clinical Pharmacology Peking University First Hospital Beijing 100034 China

Background：As a time-dependent antibiotic,the time of cefazedone concentration exceeds the minimum inhibitory concentration （MIC） is the key pharmacokinetic-pharmacodynamic （PK-PD） variable associated with the killing of *** purpose of the study was to evaluate the clinical regimen rationality of intravenous cefazedone sodium in the treatment of community-acquired pneumonia （CAP） by PK/PD ***：Ten patients with mild to moderate CAP were enrolled to receive intravenous cefazedone sodium （2 g q12 h） for 7-14 *** samples were collected in any day during day *** specimens were collected before treatment for bacteria isolated,and susceptibility to cefazedone ***-PD analysis was performed using the noncompartmental analysis of Phoenix WinNolin software （version 6.1,Pharsight Corporation,CA,USA）.The maximal time above MIC （fT ＞ MIC） was calculated,and its correlation with clinical efficacy was ***：All 10 patients completed the study and 8 of them were *** strains were isolated from patients before treatment （one for each patient） and all susceptible to *** patients of six in culture positive group were *** pathogens were cleared at the end of *** MICs were between 0.25 and 1 mg/*** main PK parameters were Cmax 175.22 ± 36.28 mg/L;T1/2 1.52 ± 0.23 h;AUC（0-∞） 280.51 ± 68.17 mg·L1·h1;CL 7.37 ± 1.84 L/h;Vd 16.06 ± 4.42 *** average fT＞MIC was 55.45±8.12％.Conclusions：Intravenous injection of cefazodone sodium with 2 g q12 h dosage regimen is used in the treatment of CAP caused by sensitive bacteria,either fT＞MIC or clinical efficacy shows that such dosing regimen is reasonable.

关键词： Cefazedone Community-acquired Pneumonia pharmacodynamic Pharmacokinetic

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A single dose pharmacokinetic and pharmacodynamic study of MEDI3617 in cynomolgus monkeys

A single dose pharmacokinetic and pharmacodynamic study of M...

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2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛

作者： LIU Yong-zhen WU Chi-yuan LU Hong YU Hong REN Jin Centre for Drug Safety Evaluation and Research Shanghai Institute of Materia Medica

OBJECTIVE MEDI3617 is a candidate pharmacological agent under development by *** study is designed to assess pharmacokinetic profiles and to fully characterize total and free angiopoietin-2(Ang2) responses after a single intravenous(Ⅳ) administration in cynomolgus *** Four male naive cynomolgus monkeys were assigned to this *** animals were given a single dose of 6 mg·kg MEDI3617 viaⅣadministration for approximately 30 *** recovery period was 56 *** samples were taken at different time points to assess exposure of MEDI3617 and to fully characterize total and free Ang2 responses after a single IV *** Peak serum MEDI3617 concentration was attained generally at the first PK time point(1 h) post IV administration and declined biphasically *** observed mean values for maximum concentration was(213±38)mg·L,area under the serum concentration-time curve from time 0 to infinity was(1280±288)mg·L·d,clearance was(4.87±1.15) ml·kg? d,and half-life was(3.25±0.672)*** changes in free Ang2 levels were *** Ang2 concentrations were suppressed immediately after dosing(1 h) and quickly recovered back to baseline after approximately 12 *** Ang2 concentrations accumulated with a maximum accumulation of approximate 100 fold from baseline and recovered back to baseline after approximately 56 d after dosing.

关键词： pharmacokinetic MEDI3617 pharmacodynamic

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Pharmacokinetic and pharmacodynamic study of DCH extract after oral administration

Pharmacokinetic and pharmacodynamic study of DCH extract aft...

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第二届国际抑郁共病暨第十二届中国中西医结合基础理论学术研讨会

作者： Zhang xianhua Huang Xi Department of Clinical Pharmacology Xiangya HospitalCentral South University Institute of Clinical Pharmacology Central South University

In current study,a sensitive and selective liquid chromatography-tandem mass spectrometry method was developed to quantitatively determine 5 bioactive compounds(tanshinol,ferulic acid,protocatechuic acid,rosmarinic acid,salvianolic acid B) in rat plasma and qualitative detect multi-components in rat hippocampus,prefrontal cortex,and cerebrospinal fluid(CSF)simultaneously following oral administration of DCH extract(20 g/kg).This investigation was also designed to verify the expected preventive effect of cerebral ischemia injury after oral administration of DCH *** separation was carried out on an 300 SB-C18 column using a gradient elution with a mobile phase composed of acetonitrile-water(containing0.1%formic acid) at a flow rate of 1.0 mL/*** mass spectrometry(MS) determination was conducted in the multiple reaction monitoring(MRM) mode with negative electrospray *** validated method exhibited good linearity with correlation coefficients greater than 0.9949 over a wide concentration range and the lower limits of quantification were 2.09-12.2 ng/ml for the 5 *** assay was successfully applied to investigate the pharmacokinetics of 5 compounds in rat plasma after oral administration of DCH *** pharmacodynamics study,the result of neurological deficit and infarct volume suggested DCH extracts could exert the preventive effect in cerebral ischemia injury.

关键词： DCH extracts pharmacokinetic LC/MS/MS pharmacodynamic cerebral ischemia injury

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Population pharmacokinetic and pharmacodynamic evaluation of Xuesaitong injection,a typical multiple constituent tradition Chinese medicine in patients with cerebral ischemia

Population pharmacokinetic and pharmacodynamic evaluation of...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： LI Xiao-yu~(1,2) WANG Guang-ji~2 XIONG Yu-qing~3 SUN Jian-guo~2 HAO Hai-ping~2 ZOU Lang~4 ZHENG Yuan-ting~2 YAN Bei~2 XIA Chun-hua~(2,3) LIU Gao-lin~1 1 Department of Clinical Pharmacy,Affiliated First People Hospital of Shanghai Jiaotong University,Shanghai 200080,China 2 Key Laboratory of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,Jiangsu,China 3 Institute of Clinical Pharmacology,Medical College of Nanchang University,Nanchang 330006,Jiangxi,China 4 Department of Clinical Medicine,Jiangxi College of TCM,Nanchang 330004,Jiangxi,China

AIM:Pharmacokinetic and pharmacodynamic profiles of Xuesaitong injection in cerebral ischemic patients are in- vestigated in order to optimize dosage regimen of muhiple constituent TCM in clinic. METHODS:63 patients were studied in our protocol. Enumeration and measurement data of all patients were collected during our *** samples were col- lected for two times at different time after intravenous infu- sion Xuesaitong injection at the dosage of 800 mg/kg for two *** of Xuesaitong injection in plas- ma,prothrombin time(PT),thrombin time(TT),activat- ed partial thromboplastin time(APTT)and fibrinogen(Fib) were *** and SAAM Ⅱ were employed for the simulation of PPK parameters and time-course fit- ting of Xuesaitong injection in cerebral ischemic patients. RESULTS:Population pharmacokinetic(PPK)parame- ters of Xuesaitong injection obtained as follow:CL:1.5 L·h(-1)·kg(-1),CL:13.0 L·h(-1)·kg(-1),k:0.1136/ h,k:0.9848 /h,k:0.2057 /***-individual variability were 36.3 %,17.8 %,1.0% and 60.3 %. Residual variability was 8.67%.Age,stature,gender of patients showed no correlation with the prolong ratio of PT (PT%),TT(TT%),APTT(APTT%)and inhibit ratio of Fib(Fib%)whereas dosage(weight),infusion ratio anti concentration of Xuesaitong injection in plasma were marked correlation to PT%,TT%,APTT% and Fib%. Correlation coefficient between dosage,infusion ratio, plasma concentration to PT%,TT%,APTT% and Fib% were 0.598,0.551,0.590,0.505;0.204,0.401, 0.348,0.403 and 0.560,0.436,0.593,O.351,re- spectively.P value was less than 0.01 or *** pharmacological effect obtained when Xuesaitong injection was administered as follow:Dosage was of 12.0-17.0 mg/kg,infusion ratio was of 10.0-18.0 mg/min and plasma concentration was of 25.0-35.0 μg/*** course of Xuesaitong injection in cerebral ischemic patients was successfully predicted and simulated results suggested that better effects were obtained at the dosage of 800- 1200 mg/d than 200-40

关键词： population pharmacokinetic(PPK) pharmacodynamic traditional Chinese medicine(TCM) dosage regimen optimization

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Pharmacokinetic,pharmacodynamic,and efficacy profiles of ergosta-4,6,8(14),22-tetraen-3-one,a natural product with diuretic activity from Polyporus umbellatus

Pharmacokinetic,pharmacodynamic,and efficacy profiles of erg...

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中药与天然药高峰论坛暨第十二届全国中药和天然药物学术研...

作者： Ying-Yong Zhao~(a,*),Xian-Long Cheng~b,Feng Wei~b,Rui-Chao Lin~b,Shuang-Cheng Ma~(b,*) a Key Laboratory of Resource Biology and Biotechnology in Western China,Ministry of Education, the College of Life Sciences,Northwest University,No.229 Taibai North Road,Xi’an,Shaanxi 710069,P.R China b Institute for the Control of Chinese Traditional Medicine and Ethnic Medicine,National Institute for Food and Drug Cotrol,Beijing 100050,P.R.China

The aim of the present study was to characterize the pharmacokinetic, pharmacodynamic,and efficacy profiles of ergosta-4,6,8(14),22-tetraen-3-one(ergone)from Polyporus *** pharmacokinetic study was carried out to determine plasma concentration of ergone in rats after oral administration at a dose of 20 mg/*** amount of ergone in plasma was measured by HPLC/*** pharmacodynamic study was carried out to evaluate the diuretic effects after oral/intraperitoneal adrninistration of 2.5,20 mg/kg of *** established method was applied for the pharmacokinetics study of ergone in six rats with the mean values of C,T,AUC,***/F,and V/F of ergone after oral administration a single 20 mg/kg dose obtained were 1.29μg/mL,3.41 h,13.7μg h/mL,3.32 h,1.98 1/h/kg,and 9.25 1/kg,respectively. The high-dose ergone provoked a significant increase in urine output and urinary excretion of K, Na and Cl after oral/intraperitoneal *** urinary rate of sodium excretion was parallel to the ergone concentration of plasma curve throughout the period under *** summary,these data suggest that ergone induced significantly greater diuretic and natriuretic effects after oral *** was also a linear relationship between ergone plasma concentration and rate of sodium excretion.

关键词： Polyporus umbellatus Ergosta-4,6,8(14),22-tetraen-3-one Pharmacokinetics pharmacodynamic Diuretic effect

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A single dose pharmacokinetic and pharmacodynamic study of MEDI3617 in cynomolgus monkeys

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中国药理学与毒理学杂志 2013年第3期 544-544页

作者： LIU Yong-zhen WU Chi-yuan LU Hong YU Hong REN Jin Centre for Drug Safety Evaluation and Research Shanghai Institute of Materia Medica MedImmune LLC.HaywardCA 94545USA

OBJECTIVE MEDI3617 is a candidate pharmacological agent under development by *** study is designed to assess pharmacokinetic profiles and to fully characterize total and free angiopoietin-2(Ang2) responses after a single intravenous(IV) administration in cynomolgus *** Four male naive cynomolgus monkeys were assigned to this *** animals were given a single dose of 6 mg·kg-1 MEDI3617 via IV administration for approximately 30 *** recovery period was 56 *** samples were taken at different time points to assess exposure of MEDI3617 and to fully characterize total and free Ang2 responses after a single IV *** Peak serum MEDI3617 concentration was attained generally at the first PK time point(1 h) post IV administration and declined biphasically *** observed mean values for maximum concentration was(213 ± 38) mg·L-1,area under the serum concentration-time curve from time 0 to infinity was(1280 ± 288) mg·L-1.d-1,clearance was(4.87 ± 1.15) ***-1.d-1,and half-life was(3.25 ± 0.672) *** changes in free Ang2 levels were *** Ang2 concentrations were suppressed immediately after dosing(1 h) and quickly recovered back to baseline after approximately 12 *** Ang2 concentrations accumulated with a maximum accumulation of approximate 100 fold from baseline and recovered back to baseline after approximately 56 d after dosing.

关键词： pharmacokinetic MEDI3617 pharmacodynamic

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Pharmacia and biological functionalities of nutrient broth dispersed multi-walled carbon nanotubes:A novel drug delivery system

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Science China Chemistry 2010年第3期53卷 611-617页

作者： Li, Di Xiao, Sai Jin Huang, Cheng Zhi Key Laboratory on Luminescence and Real-Time Analysis Ministry of Education College of Chemistry and Chemical Engineering Southwest University Chongqing 400715 China College of Pharmaceutical Sciences Southwest University Chongqing 400715 China

A new drug delivery system was developed using the interaction of nutrient broth treated multi-walled carbon nanotubes(NBT-MWCNTs) and cefotaxime sodium(CTX) as a *** factors of the drug delivery system include dispersion effect,biocompatibility of NBT-MWCNTs,pharmacodynamic effect and delivery efficiency in *** was found that MWCNTs can be well dispersed in the nutrient broth and stable at least for one week at 4 °*** formed NBT-MWCNTs suspension scarcely exhibits toxicity to *** at concentrations lower than 10.24 μg/mL,but displays enhanced pharmacodynamic effect of CTX via its bridge effect and targeted *** with general acid treated MWCNTs(AT-MWCNTs),our present NBT-MWCNTs show good biocompatibility,enhanced pharmacodynamic effect,and high delivery efficiency.

关键词： drug delivery system multiwalled carbon nanotubes biocompatibility pharmacodynamic effect flow cytometry

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