Table of Content

Volume 12 Issue 4
26 April 2007

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Consideration of pharmacogenomics in individualized therapy on clinical practice

LI Jin-heng

2007, 12(4):  361-365. 

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Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of many medications.Pharmacogenomics is to study of how genes affect the individual response to drugs.There are some evidences that in the future the use of pharmacogenomics could help to enhance the effects of drugs and reduce the adverse drug reactions (ADRs), as it aims to predict which patients are likely to respond to a particular drug and which patients are likely to have significant ADRs.Pharmacogenomics studies are rapidly elucidating the inherited nature of these differences in drug disposition and effects, thereby providing a strong scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.In this article some examples of genetic polymorphisms which affecting drug pharmacokinetics (in protein binding of drugs in plasma) and pharmacodynamics (correlated with antihypertensive drugs) are briefly illustrated.

Natural antioxidants-new approaches for suppressing cancer metastasis

YANG Jing-ya, WU Hong-zhong, HU Yi, FENG Jun, LIU Jian-wen

2007, 12(4):  366-370. 

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Metastasis is one of the major causes of mortality in cancer patients.The complicated multistep processes of cancer metastasis are involved, refer to gene, extracellular matrix (ECM), motility of cancer cells and angiogenesis.Reactive oxygen species (ROS) is related to each process of metastasis and can promote metastasis of tumour cells.Antioxidant represses the cancer metastasis through scavenging ROS.It is important to develop high performance, non-toxic natural drug from natural antioxidant to inhibit cancer metastasis.The exploration of compounds from polyphenols, flavonoids, terpene, and vitamins may lead to finding new drug for antimetastasis.

Remodeling of intrarenal small arteries

HUANG Xin-tao, HONG Hua-shan

2007, 12(4):  371-375. 

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Vascular remodeling is not only the pathologic cause of circulation dysfunction and vascular disease such as hypertension and diabetes, but also can accelerate the process of dysfunction and failure of target organs.To reverse vascular remodeling has been one of the clinical aims.Kidney is one of the critical common target organs of many kinds of diseases such as diabetes and hypertension. The main part of the intrarenal resistance comes from the intrarenal small arteries, and the remodeling of intrarenal small arteries can reduce the blood supply of kidney and lead to excessive activation of neuroendocrine system as well their vicious cycle, resulting a terrible prognosis together with kidney and other target organs failure.This paper reviews the advance of vascular remodeling especially in the intrarenal small arteries.

Advances in studies of angiogenesis inhibitor

HUANG Wei, GUAN Yong-biao

2007, 12(4):  376-380. 

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Angiogenesis is essential for cancer growth and metastasis, which is a crucial process as it furnishes tumor cell with enough nutrients and oxygen.Tumor size can be reduced and metastasis of tumor be blocked if the formation of new blood vessel networks is prevented.As the features of angiogenesis inhibitors are of low toxicity and have less acquired resistance, it comes to a new strategy to suppress tumor growth by restraining angiogenesis.

Effects of maslinic acid as a novel glycogen phosphorylase inhibitor on cerebral ischemia in mice

GUAN Teng, LI Yun-man, SUN Hong-bin

2007, 12(4):  381-384. 

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AIM: This experiment was designed to study the protective effects of maslinic acid, a novel glycogen phosphorylase inhibitor, on cerebral ischemia in mice. METHODS: The model of acute cerebral ischemia-reperfusion in mice was set up by ligating bilateral common carotid artery and vagus, thus blocking the blood stream for 90 s, and subjecting mice to 5 min reperfusion.Brain samples were prepared to observe the cerebral injury;liver samples were prepared to observe the status of hepatic glucose metabolism, which contribute to the observed hyperglycemia during cerebral ischemia. RESULTS: Maslinic acid significantly reduced the lactate and MDA level, increased SOD and LDH activity and preserved the hepatic glycogen after mice were subjected to acute cerebral ischemia-reperfusion. CONCLUSION: Maslinic acid may exert its potential protective effects against cerebral ischemic injury, at least in part, through inhibition of over degradation of cerebral glycogen and thus reducing/Lactate production during ischemia.

Determination of bencycloquidium bromide, a novel anticholinergic compound,in rat’ s bile, urine and feces by LC-ESI-MS

XU Qin, DINg/Li, LIU Wen-ying, CHEN Xiao-ping, LI Rong-shan, SONG Qin-xin

2007, 12(4):  385-391. 

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AIM: This study was undertaken to study the excretion rule of bencycloquidium bromide (BCQB) in rats, and a LC-ESI-MS method was developed for the determination of BCQB in bile, urine and feces sample of rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) assay for the determination of BCQB in rats bile, urine and feces was firstly developed and validated.After addition of 1-ethyl-bencycloquidium bromide as an internal standard (I.S.), the biological samples were prepared by using solid phase extraction on a C18-cartridge column.Chromatographic separation was analyzed on a Hanbon Lichrospher 5-C18 column.The mobile phase consisted of methanol-40 mmol L ammonium acetate buffer-formic acid (70:30: 0.3, v v v) was pumped at 0.8 mL min for bile.The mobile phase consisted of methanol-40mmol L ammonium acetate buffer-formic acid (75:25:0.25, v v v) was pumped at 1.0 mL min for urine and feces.LC-ESI-MS was carried out on a single quadrupole mass spectrometer using electrospray ionization (ESI) and positive selectedion monitoring (SIM).Target ions were monitored at [M] + m z 330.2 for BCQB and [M] +m z 344.2 for I. S.. RESULTS: The extraction recoveries of BCQB in bile, urine and feces were upper 77 %.The RSD of intrarun and inter-run precisions were all below 15 %.The calibration curves were linear over the concentration ranges of 30.15-1507.50 ng mL (r =0.9995) for the BCQB in bile, and the low limit of quantitative (LLOQ) was 30.15 ng mL.The calibration curves were linear over the concentration ranges of 3.02-1507.50 ng mL (r = 0.9997) for the BCQB in urine, and the LLOQ was 3.02 ng mL.The calibration curves were linear over the concentration ranges of 3.02-1507.50 ng mL (r =0.9997) for the BCQB in feces, and the LLOQ was 3.02 ng mL. CONCLUSION: The method is specific, accurate, reliable and sensitive.The established method has successfully been applied to study the excretion of BCQB in rats after intranasal administration.

Dexamethasone suppressed over-activated endothelin system in chronic heart failure rats via anti-oxidative stress effect

NA Tao, DAI De-zai, TANG Xiao-yun, DAI Yin

2007, 12(4):  392-395. 

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AIM: To investigat over-activated endothelin (ET) signaling and oxidative stress in chronic heart failure (CHF) rats and dexamethasone intervention. METHODS: Rats were performed left coronary artery ligation for 6 weeks to develop CHF and treated with dexamethasone.Masson's trichrome was used to measure myocardial fibrosis.mRNA expression of endothelin A receptor (ETA R), NF-κB and inducible nitric oxide synthase (iNOS) in myocardium were performed. RESULTS: Myocardial fibrosis was more obvious in CHF group than that in sham operation group.Dexamethasone treatment ameliorated interstitial fibrosis in myocardium of CHF rats.mRNA expression of ETAR, NF-κB and iNOS in myocardium of CHF rats was significantly upregulated compared with sham operation group, and dexamethasone down-regulated the mRNA expression of ETAR, NF-κB and iNOS. CONCLUSION: Dexamethasone inhibits over-activated ET signaling and oxidative stress in CHF myocardium through the down-regulated ETAR, which attenuate myocardial fibrosis.

Hepatotoxicity and its mechanism of saikosaponin d on the human liver LO2cells in vitro

LI Tao, JIANG Zhen-zhou, WANG Tao, ZHANg/Lu-yong, XU Xiao-yue, JIA Xiao-ming, MIAO Wen-ying, MIN Chao

2007, 12(4):  396-400. 

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AIM: This study was to determine whether saikosaponin d (ssd)caused hepatotoxicity and to investigate the possible toxicity mechanism. METHODS: Experiment was carried out using the human live cell lines (L-O2)in vitro.MTT assay, change of cellular morphology, DNA fragmentation analysis, nuclear staining with 4, 6-diamidino-2-phenylindole (DAPI), hemolysis assay and membrane leakage of lactate dehydrogenase (LDH assay) were adopted to evaluate the hepatotoxicity of ssd. RESULTS: Results showed that L-O2 cells were inhibited significantly by above 2.5 μmol/L ssd, and IC50 = 2.44 μmol L.The change of celluar morphology, increase of LDH release and hemolytic ratio (%)could be detected significantly when treated with 5 μmol/L ssd. However, other results showed no obvious induction on the apoptosis from DNA ladder and DAPI. CONCLUSION: The toxicity mechanism of ssd on the L-O2 cells in vitro might be not through apoptosis, but related to the cytolysis.

Studies on human mesenchymal stem cells differentiation into cardiomyocytes in vitro

LI Ning, HOU Xiang-lin

2007, 12(4):  401-404. 

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AIM: To study the mechanisms of the human mesenchymal stem cells differentiating into cardiomyocytes induced by 5-azacyditine. METHODS: The mesenchymal stem cells were separated and purified in vitro, then given 5-azacyditine at three concentrations and at different incubation time.The vitality of the mesenchymal stem cells were assayed with the methylthiazolyl tetrazolium method in order to estimate the best concentration and incubation time.The induced cells were checked by transmission electron microscope, immunohistochemistry and RT-PCR. RESULTS: The induced cells changed their morphology to that of cardiomyocyte type. Transmission electron microscope revealed striation.Some cells were positive expression of α-sarcomeric actin, troponin-T and cardiac specific transcript factors GATA-4, Nkx2.5. CONCLUSION: The huaman bone marrow-derived mesenchymal stem cells possesses the multiple differentiation potential and can be induced to cardiomyocytes by 5-azacyditine in vitro.

Toxicity of Radix Asteris, Flos Farfarae and their combination

ZHANG Jian-wei, DOU Chang-gui, ZHANG Mian, MA Shi-ping, HUANG Fang

2007, 12(4):  405-411. 

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AIM: This study was undertaken to investigate the toxicity and pharmacological effects of Radix Asteris (RA), Flos Farfarae (FF) and the mixture of RA and FF (1:1, w w) with a view to analyzing the relation of compatibility between RA and FF. METHODS: Acute toxicity effects were measured by experimental data of half-lethal dose (LD50) or maximal tolerated dose (MTD) of mice.Hepatic injury effects were measured by experimental data of coefficient of liver, levels of ALT and AKP in serum and those of LDH and AKP in liver homogenate tissue of mice.Histopathologic examination of mice liver was also carried out.The anti-tussive, anti-asthmatic and expectorant effects were observed by concentrated ammonia method in mice, SO2 method in mice, phenolsulfonphthalein excretion volume in mice, trachea cilia movement of pigeon in vivo and the contraction of tracheal strips of guinea pig in vitro. RESULTS: LD50 of RA was 54.1 g/kg for mice.RA obviously increased the levels of ALP and AKP in serum and those of LDH and AKP in liver homogenate tissue of mice, and significantly injured the liver's tissue.MTD of FF was 136 g/kg for mice, about 755.6 times as clinical dose.The combinative group obviously degraded the injuries on liver of mice comparing with RA groups.Compared with two individual drugs, the mixture played a more prominent role in reducing tussive times caused by ammonia and SO2 in mice, promoting phenolsulfonphthalein excretion of mice and trachea cilia movement of pigeon in vivo disengaging the contraction of tracheal strips of guinea pig in vitro. CONCLUSION: The mixed RA with FF can significantly lower the toxicity of RA and strengthen pharmacological effect of two individual drugs, indicating that the mixture of RA and FF is provided with detoxicant and mutual promotion effect.

Tetrandrine induces and sensitizes vascular smooth muscle cell apoptosis in renovascular hypertensive rats

ZHANG Li, ZHANG Chang-ping, LI Qing-ping

2007, 12(4):  412-416. 

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AIM: To determine whether apoptosis is involved in the development of vascular remodeling in renovascular hypertension rats and whether the inhibitory effect of tetrandrine on proliferation is mediated by apoptosis. METHODS: Apoptosis was detected in histologic sections of aorta and tail arteries with in situ end-labeling.The apoptosis ratio in cultured cells was measured by [3H]-TdR incorporation and flow cytometer analysis method. RESULTS: Compared with the sham group, the apoptosis rate of renal hypertension rat (RHR) increased. Tetrandrine (Tet) directly induced apoptosis in cultured AVSMCs (from RHR) and increased apoptosis induced by TGFα, TGFβ1 and deficient FCS. CONCLUSION: Tet induces and sensitizes vascular smooth muscle cells of RHR to apoptosis, which at least partly related to the regression of vascular remodeling.

Effective fractions A and B from enzyme-digested colla corri asini on hematopoietic recovery in γ-irradiated mice

WU Hong-zhong, YANG Fang, CUI Shu-ya, QIN Yu-feng, ZHANG Yuan-xing, LIU Jian-wen

2007, 12(4):  417-421. 

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AIM: To further understand the hematopoietic activities and mechanisms of fraction A (1.0 g/kg and 2.0 g/kg) and B (0.8 g/kg and 1.6 g/kg) from enzyme-digested colla corri asini on the anemic mice caused by 3.5 Gy γ-irradiation. METHODS: The fraction A and B were orally administrated to the anemic mice for 25 days.After confirming the protective effects of fraction A and B, we examined the effects of fraction A and B on CFU-GM, BFU-E, CFU-E in the bone marrow and spleen, cytokines in the serum, CUF-S in the spleen, ROS in bone marrow cells, SOD and GSH-Px in serum and liver homogenate. RESULTS: Fraction A administrated at 2.0 g/kg and 1.0 g/kg and fraction B administrated at 1.6 g/kg and 0.8 g/kg activated granulocyte and erythrocyte progenitor cells in bone marrow and spleen, led to the recovery of white blood cell and red blood cell count to a value that is almost approaching the basal level, increased the colony number of CFU-GM, BFU-E, CFU-E in bone marrow and spleen, stimulated the CFU-S in the spleen, significantly stimulated the secretion of IL-6 and GM-CSF, decreased the ROS level in bone marrow cells, and increased the SOD activity in bone marrow and liver and GSH-Px activity in serum. CONCLUSION: These results suggest that the fraction A and B from the enzyme-digested colla corri asini promote hematopoiesis by activating immature granulocyte and erythrocyte cells, in part by stimulating the GM-CSF and IL-6 secretion and elevating the ROS scavenging ability.

Effects of various of resuscitation fluids on expression of soluble cell adhesion molecules in rats with hemorrhagic shock

WANG Xiao-rong, PAN Jing-ye, ZHU Ye-fan, WANG Ming-san, SHEN Zhi-jian, LIN Xi-fang, LIN Sui-chai, CHEN Jie

2007, 12(4):  422-426. 

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AIM: To investigate the changes of blood soluble adhesion molecules during hemorrhagic shock in rats and the effects of various of resuscitation fluids on expression of blood cell adhesion molecules in rats with hemorrhagic shock. METHODS: 50 SD rats were divided into 5 (control, sham, shock, lactated Ringer's and 6 % hydroxyethylstarch) groups randomly.Lactated Ringer's group and hydroxye-thylstarch group were subjected to hemorrhagic shock for 1 h, followed by resuscitation with lactated Ringer's solution and 6 % hydroxyethylstarch for 2 h by three times of the lost blood.After resuscitation, the GMP-140, sVCAM-1 and sICAM-1 were measured.At the same time, the control, the shock and the sham groups were drawn the blood to test. RESULTS: Blood plasma GMP-140, sVCAM-1 and sICAM-1 in the shock group were significantly higher than those of the control and sham group (P<0.01).Blood GMP-140, sVCAM-1 and sICAM-1 in Lactated Ringer's group were higher than those of the control group (P<0.01). Plasma GMP-140 in Lactated Ringer's group were higher than that of the sham group (P<0.01).Serum sVCAM-1 in Lactated Ringer's group was higher than that of the shock group (P<0.01).Compared with the shock group and Lactated Ringer's group, the GMP-140, sVCAM-1 and sICAM-1 were reduced in the hydroxyeth-ylstarch group (P<0.01). CONCLUSION: It is concluded that hemorrhagic shock triggers the coagulation cascade reaction, and the coagulation of the actors is greatly consumed.Unbalance of coagulation system plays an important role in the progress of shock.Resuscitation with 6 % hydroxyethylstarch may reduce the inflammatory response in rats undergoing hemorrhagic shock compared to a crystalloid-based volume therapy.Hypothesize that this is most likely due to an improved microcirculation with reduced endothelial activation and less endothelial damage.

Determination of evodiamine by high performance liquid chromatographytandem mass spectrometry and pharmacokinetic studies in rats

XU Ji-hua, LIU Wen-ying, ZHENG Feng, SUN Di, YANG Qian, RAO Jin-hua

2007, 12(4):  427-433. 

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AIM: To establish an LC-MS MS method for determination of evodiamine concentration in rat plasma and to study its pharmacokinetic profile in rats. METHODS: Six rats were administrated (i.g.)evodiamine at the dose of 100 mg/kg.Blood samples were collected from eye socket.Evodiamine concentration in rat plasma was determined by LC-MS MS method.The pharmacokinetic parameters were calculated using DAS program. RESULTS: A good linear relationship was obtained in the concentration range (0.2-50.0 ng mL) studied (r2 =0.9997).Average recoveries ranged from 96.12 % to 99.46 %.Intra-and inter-day relative standard deviations were 4.61 %-13.51 % and 5.65 %-11.49 %, respectively.The main pharmacokinetic parameters of evodiamine were as follows:C_max(5.3±1.5) ng mL;t_max(22±8)min;t 1 2(451±176)min. CONCLUSION: A selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS MS)method for the quantification of evodiamine in rat plasma is developed and validated.This method is successfully applied for the pharmacokinetic studies of evodiamine in rats.

Pharmacokinetics and in vitro-in vivo correlation evaluation of selfemulsifying drug delivery system and conventional tablets of aniracetam

LI Juan, ZHANG Yan, WANG Guang-ji

2007, 12(4):  434-439. 

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AIM: To evaluate the correlation between in vitro release and in vivo absorption of aniracetam in conventional tablets and self-emulsifying drug delivery system (SEDDS), to investigate pharmacokinetics of aniracetam self-emulsifying drug delivery system and conventional tablets of aniracetam after oral administration to rats. METHODS: Dissolution behavior of these formulations was evaluated in vitro to assess the properties of dosage forms.And a new RP-HPLC method was developed for the in vivo quantitative determination of 4-p-anisamidobutyric acid (PABA), the active metabolite of aniracetam.To approach the in vitro-in vivo correlation, fraction absorbed in vivo (f) was calculated by Wagner-Nelson method, and then compared with in vitro released drug percentages (Q %). RESULTS: Aniracetam was released rapidly from SEDDS with 80 %±4 %of accumulation dissolution rate compared to that from conventional tablets at 15 min.The recovery of active metabolite of aniracetam was about 90 %, and the intra-days and interday precision were within 4 % and 6 %, respectively.The AUC0-∞ value of aniracetam SEDDS was (11 168±2 395) ng·mL-1 ·h, which was about 3 folds greater than conventional tablets.The parameter MRT0-∞ of aniracetam SEDDS and conventional tablets were (2.7±0.6) h and (1.7±0.6) h, respectively, and the difference was statistically significant(P<0.05).The linear equation of in vitro-in vivo correlation for conventional tablets was obtained by regression as well.Whereas nonlinear correlation was obtained for aniracetam SEDDS, which fitted the quadric model very well and the correlation coefficient was 0.972. CONCLUSION: Aniracetam can be released faster from SEDDS than that from conventional tablets, and SEDDS improved the bioavailability of aniracetam significantly.The SEDDS composed by oil and compound surfactants which could enhance the absorption showed the expressing rate of dissolution, and those formed the o w microemulsion with gastrointestinal liquid could absorb through lymphatic transport route.

Protective effects of picroside Ⅱon glutamate injury of PC12 cells

GUO Ming-chuan, CAO Yan, LIU Jian-wen

2007, 12(4):  440-443. 

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AIM: To investigate the effect of picroside Ⅱ on apoptosis induced by glutamate. METHODS: After being treated with picroside Ⅱ and glutamate, the viability of PC12 cells was detected by MTT assays, and CDCFH was used to detect the reactive oxygen species (ROS).The apoptosis rate was measured by DNA fragmentation agarose gel electrophoresis;The expression of Bcl-2 was detected by Western blot. RESULTS: Picroside Ⅱ could significantly protect PC12 cells from the apoptosis induced by glutamate, increase cell survival rate, decrease the level of intracellular ROS and upregulate Bcl-2 protein expression. CONCLUSION: The underlying mechanisms may be involved in the inhibition or decreasing of ROS formation, and increasing the expression of Bcl-2.

Effects of propofol on expression of protein kinase C and calcium ion concentration in human vascular endothelial cells induced by hypoxia injury

ZU Jian-yu, DIAO Yu-gang, LIU Jie, CHEN Wei-min

2007, 12(4):  444-447. 

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AIM: To investigate the effects of propofol on the expression of protien kinase C and intracellular calcium homeostasis in human vascular endothelial cells induced by hypoxia-reoxygenation injury. METHODS: The endothelial cells were separated from human umbilical veins.The cells were cultured in normal medium or the medium containing different concentrations of propofol. The cells were further incubated in hypoxic condition for 30 min and then in normal condition for 6 h to induce hypoxia-reoxygenation injury.The cells were divided into groups:the control group (C group), the hypoxia-reoxygenation group (HR group) and propofol groups (PR 25, 50, 100 μmol L groups).The expression of PKC and the concentration of intracellular calcium were measured by Western-blot analysis and immunofluorescence method, respectively. RESULTS: The number of apoptosis increased after reoxygenation (14.7±1.0 %).Propofol inhibited the apoptosis significantly (P<0.01), and the inhibited effect of propofol on 50 μmol L(9.4±0.6) % and 100 μmol L(9.5±0.6) %was more significant compared with the propofol on 25 μmol L(12.3±0.7) % (P<0.01).The expression of PKC was significantly inhibited after reoxygenation (P<0.01).The concentration of intracellular calcium induced by hypoxia-reoxygenation injury was up-regulated (117.3±6.0) %.Propofol attenuated the concentration of intracellular calcium significantly (P<0.01) and was more effective at 50 and 100 μmol L (P<0.01).Propofol at a concentration of 25 μmol L could significantly (19.0±1.7) %upregulate the expression of PKC (P<0.01).Propofol at concentrations of 50 μmol L (27.0±2.4) % and 100 μmol L (27.5± 2.6) % showed a similar result but is significant compared with PR25 group (P<0.01). CONCLUSION: Hypoxia-reoxygenation injury induces apoptosis, which may be related to inhibiting the expression of PKC and increasing the concentration of intracellular calcium.Propofol inhibits the apoptosis of endothelial cells induced by hypoxia-reoxygenation injury, and the mechanism is possibly related to the activation of PKC and depression of calcium overload.

New software for carrying out data analysis of bioavailability and bioequivalence testing

CHEN Zhi-yang, XIE Hai-tang, SUN Rui-yuan, HU Gang

2007, 12(4):  448-454. 

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Generic drug products (test products: drug A, B...) are bioequivalent to an innovator product (reference product) when their bioavailabilities in the same molar dose are similar.Bioavailability is usually expressed by following pharmacokinetic parameters:the area under plasma concentration-time curve (AUC), the maximum plasma concentration (C_max) and the time of maximum plasma concentration (t_max).This paper used a two period crossover bioequivalence study to develop convenient, friendly user interface software, BA&BE Analysis to statistically process data in clinical pharmacology studies and other areas.The method involves user input of data for analysis into a grid format, setting variables and parameters, followed by one-way analysis of variance (ANOVA), bioavailability and bioequivalence analysis of the data.The software developed in the present study should help scientists to carry out data analysis of bioavailability and bioequivalence testing quickly and easily.

Electronic data capture:achieving the promise of more efficient and higher quality clinical trials

BO Qing-yan, XIONG Ning-ning, ZOU Jian-dong, JIANG Meng, LIU Fang, WANG Xiu-qin, GAO Wei-min

2007, 12(4):  455-459. 

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Electronic data capture (EDC)is a technique for collecting clinical trial data in such a way that they are delivered to the sponsor in electronic form instead of on paper.Web-enabled EDC will become the fundamental mode for clinical trial data capture in the future. Source data of EDC includes paper source data and electronic source data.Source data verification (SDV)of the former one is evaluating the conformity of the data presented in e-CRF with source data.Although electronic source data eliminates need for SDV, strict logic check at the time of data entry and investigating audit trials are needed to confirm the authenticity of the data.EDC may realize cost saving and improvement of efficiency and data quality, as well as addressing some problems in PDC based clinical trial.

Distribution of UGT1A9 C-2152T and UGT2B7 G211T mutants in Chinese Han population

YI Juan, XIE Hai-tang, ZHOU Hong-hao

2007, 12(4):  460-464. 

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AIM: Detection of UGT2B7 G211T and UGT1A9 C-2152T variant alleles, and knowledge about their allelic frequency in a Chinese population. METHODS: To determine the allelic frequency of the UGT1A9 C-2152T in a group of 100 Chinese male subjects by using of touch-down polymerase chain reaction-restriction fragment length polymorphism (Touch-down PCR RFLP) assays.To determine the allelic frequency of the UGT2B7 G211T mutant in a group of 363 Chinese subjects by using of polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) assays. RESULTS: The frequency of the UGT1A9 C-2152T mutant allele was rare in a Chinese population which was similar to that of Asian people.In a group of 363 unrelated individuals, the frequency of the UGT2B7 G211T mutant in Chinese population was 0.158, which was similar to that of Japanese.The allelic frequency in Chinese male was 0.128, which was statistically higher than that of Chinese female 0.110. CONCLUSION: We have found a PCR-RFLP assay for genotyping UGT2B7 G211T mutant.This straightforward and prompt PCR-RFLP assay has a good reproducibility, and therefore can be used to genotype for the UGT2B7 G211T polymorphism in a large population samples.The frequency of the UGT2B7 G211T mutant allele is high in a Chinese population.

Clinical trial report of two doses of pemirolast potassium

XU Qin-e, LIN Zi-ping, LI Ze-qing, YU Ying-ying, MA Wei-yang, YUE Zhi-yong, SHI Li, XUE Wei-guo, ZHAO Jun, CHAI Yi, YU Hao, ZHANG Yin-di, SHEN Jian-ping

2007, 12(4):  465-469. 

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AIM: Using 100 mg tranilast as control, to investigate the clinical safety and effect of 5 mg or 10 mg pemirolast potassium which is for the treatment of allergic rhinitis. METHODS: Patients in the trial groups took pemirolast potassium 5 mg or 10 mg orally after breakfast and supper daily for 4 weeks.Patients in control group took tranilast 100 mg, and the usage and course of treatment were the same as trial groups.20 male volunteers took pemirolast potassium 10 mg once a day. RESULTS: Pemirolast potassium 5mg had a better effect for treatment of allergic rhinitis than tranilast 100 mg (P< 0.01).Pemirolast potassium 5 mg had a similar curative effect for allergic rhinitis to tranilast 100 mg.No serious drug reaction happened, and two doses of pemirolast potassium and tranilast 100 mg showed similar safety (P > 0.05). CONCLUSION: To cure allergic rhinitis, two doses of pemirolast potassium have good efficancy and safety compared to tranilast 100 mg.

Pharmacokinetics of penciclovir injection in Chinese healthy volunteers

XU Jun-yu, LIU Yu-wang, SUN Pei-hong, CUI Yi-min

2007, 12(4):  470-473. 

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AIM: To study the pharmacokinetics of penciclovir injection in Chinese healthy volunteers. METHODS: 10 healthy volunteers were infused a single dose of 10 mg/kg of penciclovir.The concentrations of penciclovir in plasma and urine were determined by HPLC-FLD.Pharmacokinetic parameters were conformed to a non-compartment model analyzed by WinNonLin program. RESULTS: The main pharmacokinetic parameters were as follows:the ke was (0.37±0.05) h;the t12 was (1.91±0.26)h;the C_max was (9.8±1.6)mg/L; the AUC_0-t was (19.1±2.8)mg·L ^-1 ·h;the AUC_0-∞ was (19.6±2.9)mg·L^-1 ·h;the Vd was (1.4±0.4) L/kg;the CL was (0.52±0.08)L·h·kg ^-1.About 70 %of penciclovir was excreted into urine within 12 h. CONCLUSION: Penciclovir is widely distributed and rapidly excreted, predominantly by the kidney..

Healthy volunteers received tested candesartan cilexetic tablet and the study of its pharmacokinetics

ZHU Yu-bing, ZOU Jian-jun, QIAN Wei, HU Yun-fang, FAN Hong-wei, XIAO Da-wei

2007, 12(4):  474-477. 

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AIM: To establish a HPLC method for determination of concentration of candesartan in human plasma and study the pharmacokinetics of the tested tablet in Chinese healthy volunteers. METHODS: 20 healthy volunteers received tested tablet (a single oral dose of candesartan cilexetic 16 and 32mg and multidose 16 mg, qd × 6 d).Candesartan concentrations in plasma were determined by HPLC. RESULTS: The main pharmacokinetic parameters of candesartan were as follows:t 1 2β were 6.6± 0.5 h, 6.8± 0.4 h and 6.6± 0.5 h;t_max were 4.1± 0.6 h, 4.5± 0.5 h, 4.4± 0.4 h;C_max were 152± 23 μg/L, 226± 39 μg/L and 166± 25 μg/L;AUC_0-36 were 1145± 478, 2416± 398 and 1282± 423 μg·h·L ^-1;MRT0-36 were 10.3± 0.5 h, 10.8± 0.7 h, 10.7± 0.3 h. CONCLUSION: The method is accurate, sensitive and reliable, and a two-compartment open pharmacokinetic model is adapted in candesartan plasma concentration-time data analysis;The main pharmacokinetic parameters of the domestic candesartan are similar to those reported abroad, so it can be extensively used in clinic.

Case reports on 6 patients with chronic myelocytic leukemia treated with complex capsules of Qinghuang

TANG Qiang, SHEN Jie, LIU Zhao-qian

2007, 12(4):  478-480. 

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AIM: To investigate the clinical effects of complex capsules of Qinghuang in the treatment of patients with chronic myelocytic leukemia (CML). METHODS: The complex capsules of Qinghuang are composed of indigo naturalis, realgar, etc.The volunteers with chronic myelocytic leukemia received the clinical therapy of complex capsules of Qinghuang.The analysis of hemogram and evaluation of survival and prognosis in patients treated with and without complex capsules of Qinghuang were observed. RESULTS: We got the entire information and data of follow-up visit of patients after they were treated with complex capsules of Qinghuang for a long time.Among 6 patients, 4 of them were complete remission (CR) and 2 were partial remission (PR), and 1 patient had survived for 16 years.All patients did not deteriorate into acute transformation phase. CONCLUSION: The complex capsules of Qinghuang have a good therapeutic efficacy on the treatment of patients with chronic myelocytic leukemia, and they have only some gentle side effects.The present study provides some clinical evidences for the treatment of CML with traditional Chinese medicine and arsenical in the future.