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Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Table of Content

    Volume 4 Issue 4
    26 December 1999
    Protective effects of total salvianolic acids on cerebral hypoxia in mice
    WU Jung-Fang, WANG Jie, ZHANG Jun-Tian
    1999, 4(4):  261-264. 
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    Aim The protective effect of total salvianolic acids (Sal) on cerebral hypoxia in mice was studied. Methods Acute cerebral hypoxia was induced by sodium nitrite sc and decapitation. The effect of Sal on acute cerebral hypoxia in mice and neuronal hypoxia injury induced by sodium dithionite in primary cultures were observed.Results Sal in the doses of 10, 20 mg·kg-1 iv protected mice against the acute cerebral hypoxia and inhibited the production of lipid peroxidation in brain tissue of mice caused by cerebral hypoxia. Sal in the doses of 1~ 10μg·L-1 reduced the rate of cell death and the content of MDA and lowered LDH content in extra-cellular bathing media in oxygen deprived cortical cultures.Conclusions Sal protects mice against cerebral hypoxia by suppressing the generation of lipid peroxide.
    Therapeutic effects of ginsenosides on ischemic kidney with acute renal failure
    CHEN Xiang-Mei, LI Feng, CHENG Qing-Li, ZHANG Ying, FU Bo
    1999, 4(4):  265-267. 
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    Aim To investigate the therapeutic effects of ginsenosides on ischemic kidneys with acute renal failure. Methods Ischemic and reperfused (I/R) rat model of acute renal failure was established by clipping right renal artery of the rat for one hour and then removing the left kidney. After reperfusion for 24 hours the serum BUN, Ser, ET-1 and. NO were detected and the renal pathologic changes were observed.Results The levels of serum BUN,Scr were significantly decreased in the treatment group as compared with those in the I/R group (P<0. 05), but they were similar as those in control group (P>0.05);The tubular lesions in the treatment group were obviously ameliorated as compared with those in the I/R group (P<0. 01).Conclusion Ginsenosides have significant therapeutic effects on ischemic kidneys with acute renal failute, in which modulation of NO by ginsenosides might be involved.
    Pharmacokinetics and relative bioavailability of gemfibrozil capsules in 12 healthy volunteers
    JIANG Tao XU, Wei-Ren
    1999, 4(4):  268-271. 
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    Aim The pharmacokinetic paramneters and relative bioavailability of capsule A (Maiwei Pharmaceutical Co Ltd, Bejjing, China) and capsule B (Xianjing Pharmaceutical, Hunan, China) were studied. Methods A single oral dose of 600 mg gemfibrozil of these two kinds of capsules was given to 12 chinese healthy male volunteers in an open,randomized crossover study. Plasma levels were determined with HPLC-UV method.Results The plasma concentration-time curve was fitted to 1-compartment open model with a first order and lag time absorption and the major pharmacokinetic parameters of capsules A and B were shown respectively as following:Cmax (32.69+5.67)and (29.41+2.60) mg·L-1;Tmax(1.01+0.14) and (1.13+0.37) h,t1/2ka(0.46士0.18) and (0.62+0.20) h;Cmax(1.11土0.32) and (1.32+0.26) h;MRT(2.14土0.27) and (2.37+0.26) h;AUC (91.7+13.2) and (82.2土 7.38) mg·h·L-1. There were no significantly differences between the pharmacokinetic parameters of capsule A and B. The relative bioavailability of the capsule A was (110土9)% as compared to the capsule B.Conclusion The two kinds of capsules have the equivalent biological effects.
    Protective effects of punax notojinseg on local cerebral ischemia in rats
    SHI Yi-Ju, WU Jun-Fang, XIA Zuo-Li, XING Guo Qing
    1999, 4(4):  272-275. 
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    Aim To study the protective effects of punax notojinseg (PNS) on local cerebral ischemia in rats. Methods Local cerebral ischemia in rats was induced by occlusion of the middle cerebral artery (MCAO) without craniectomy.Results PNS in the doses of 200 and 400 mg·k-1·d-1x 10 d significantly decreased the infarct size and brain edema and ameliorated neurologic deficits in rats subjected to MCAO for 2 or 24 hours. The same dosage of PNS could markedly increase the activity of superoxide dismutase (SOD) and decrease the concentration of malondialdehyde (MDA) and Ca2+ in the brain.Conclusions Declining free radicals and decreasing Ca2+ content in brain might be one of the important factors involved in the anti-cerebral ischemia effect of PNS.
    Establishment of a model of the vascular endothelial cell injury in SD rats
    ZHAO Jian-Hong, LIN Lin GAO Ji-Fa, CAO Hui, ZHU Fan-He, MAO Qin-Bo
    1999, 4(4):  276-278. 
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    Aim To establish a model of the vascular endothelial cell (VEC) injury in SD rats. Methods SD rats were randomly divided into the control and the model groups. The model rats were injected with adrenaline diluted to 2.5 times0.05 mg·100 g-1(tid) for 5 d continously. From the 4th d, they were irritated for 5 min in the 0°C cold-water in the middle between adrenaline injections. The control rats were given 0.9% NS as above. At 6th d, blood samples were taken from carotid arteries of the rats and the CEC counts, t-PA、PAI activities, 6 keto-PGF1 concentrations and the platelet aggregation rate(max) were detected respectively.Results In the model group, as compared with those in the control group, t-PA activity and 6-keto-PGF1. concentration decreased significantly(P<0.01,P<0.05),while the CEC count、PAI activity and the platelet aggregation rate(max) increased obviously (P<0.01).Conclusions A large dose of adrenaline in combination with cold-water itritation can cause the VEC injury in SD rats.
    Experimental study of antibiotics and anticoagu lants effection on mouse peritonaeum
    1999, 4(4):  279-281. 
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    Aim The effects of antibiotics and anticoagulants on mouse peritonaeum were observed to explore the factor of the peritoneal dialysis related sclerosing peritonitis. Methods The experimental models of peritoneal dialysis were established in mice by infusing different kind of drugs to the peritoneal cavity and the changes of the peritoneal membrane for each drug at different time were observed by the autopsy and light microscope for several weeks.Results Amikacin, Cefradine, Zinacef, Ciprofloxacin, Heparin and Urokinase could induce sclerosing changes of peritoneal membrane such as loss of peritonel mesothelum ifltration of ilammaory clls and of polirntion ibrcell.Thee changes were ireresrible efter the drugs were stoped.Conclusion The drugs commonly used in prioneal dalysis may in dfen deree resul in peioneal sclerosis.
    Therapeutic effect of "shen-bing No5" on adenine-induced chronic nephritis in rats
    ZHOU Quan-Rong, DAI Shi-Wen, WANG Xu-Ping, ZHANG Wei-Min, XU Shu-yan, XIAO Cheng-Wei
    1999, 4(4):  282-285. 
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    Aim The therapeutic effect of“shen-bing No 5”,a preparation of traditional Chinese medicine on adenine-induced chronic nephritis in rats was studied. Methods Chronic nepbritis in rats was induced by giving adenine 80 mg·kg -1·d-1 orally. The model rats were treated by“shen-bing No 5”in different dosages. Levels of urea nitrogen(BUN), creatinine (Cr), total protein(TP),and Na+ in serum and or urine were detected and the changes of kidney were obseraed.Results The “shen-bing No 5”markedly lowered the levels of urine protein in 24 hours, BUN in urine and BUN, Na+in serum (P<0. 05). The kidney weight and the index of kidney weight were significantly different (P<0.01) from those in the adenine model group. The pathological examination of kidneys showed the“ shen-bing No 5” also could alleviate the expansion of renal tubules and diminish the interstitial inflammatory cell. Conclusion “Shen-bing No 5”can improve the renal function and delay the development of chronic nephritis.
    Kinetic study of nicotinic acetycholine rceptor
    ZHANG Shou-Lan, LIN Fu-Sheng, YU Lin, LIU Min
    1999, 4(4):  286-291. 
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    Aim The kinetics of nicotinic acetylcholine receptor (N-AChR) was stadied. Methods The saturation experiments of Torpedo electric organ N-AChR were taken with 125I-a-BuTX. The results were calculated by Scatfit program. Experiments were then performed to study the kinetics of dissociation of a-BuTX and nicotine from N-AChR, respectively. When their binding reached saturation, an excess of 1000 times a-BuTX or nicotine was added. The saturation binding properties of the N-AChR extracted from leg muscles of the 13th day chick embroys and optic lobes of the 20th day chick embroys were studied. The results were calculated by Scatfit program. The othe experiments were taken to observe the competition between mcotine and 125I-a BuTX for binding with Torpedo, optic lobe and skeletal muscle of the chick N-AChRs.Results The saturation experiments of Torpedo electric organ N-AChR resulted in a Scatchard plot of hyperbola which responded to the model of two kinds of receptor with on eligand. The difference of and B max between high affinity binding site and low affinity bineing site was significant. The dissaciation experiment showed that the fast dissociation rate of tow ligands was 500 times more than that of the slow dissociation rate. This result suggested that there may be two subtype N-AChRs. The saturation binding properties of N-AChR of leg muscles and optic lobe of the chick embroys revealed a Scatchard plot of two kinds of N-AChR indicating a single type of site. The binding affinity of receptor of optic lobe was 100 times more than that of muscles. In competition for Torpedo receptor by nicotine and 125I-a BuTX, the values of ICoo were different:which suggested that two kinds of receptor sites were existent. In competition of Nicotine and 125I-a-BuTX for optic lobe and skeletal muscles of the chick N-AChR, the value ICso of skeletal muscles N-AChR was 7.7 times higher than that of optic lobe.It indicated that two kinds of N-AChR subtype existed in the optic lobe and in the skeletal muscles of chick respectively.Conclusion N-AChR of Torpedo electric organ contains two kinds of subtype receptors.N-AChR of optic lobe of chick embroys is one subtype receptor,and N-AChR of skeletal muscles of chick embroy is another subtype receptor.
    Pharmacokinetics and relative bioavailability of tramadol hydrochloride tabletin Chinese healthy volunteers
    CHEN Bo, ZENG Zhao Hong, MAO Guo-Guang, MA Yue-Ming, ZHONG Qiu
    1999, 4(4):  292-295. 
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    Aim To study the pharmacokinetics and relative bioavailabilty of tramadol hydrochloride tablet. Methods Twelve male Chinese healthy volunteers received a single oral dose of tramadol hydrochloride tablet(THT) 100mg and tramadol hydrochloride capsule(THC) 100mg in a random crossover design. Drug concentrations in plasma were determined by HPLC.Results The concentration time profile conformed to an open two-compartment model. The T1/2 and AUCo-24 of two products were (7.69+3.74) h and (7.66士3.41) h,(3100土1165) μg·h·L-1 and (3212士1260) μg·h·L-1,respectively. No significant difference was observed in pharmacokinetic parameters bet ween tested and reference preparations(P>0.05).Conclusion The THT and THC have bioequivalence.
    Effect of insulin intravenous infusion during operation on glucose metaboism in obese woman patients with insulin resistance
    LIU Zhao Fang, HUANG Bin-Hui, ZHANG He
    1999, 4(4):  296-298. 
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    Aim The honpeod tbele of boswper od lasm imwlinin in oerwown peit wutiui rinee mnd heefet of nsdinie intis awrnn ation were observed. Methods 10 pitais olnormal wihleconrr goup, group A) and 20 patients of obesity women(ASA grade Ⅰ-Ⅱ) undergoing selective surgery were investigated. The patients of obesity were randomly divided into two groups(group B and C, respectively).Groups A and B liquids without glucose, and in group Ctransfuse liquids with glucose and insulin(4g glucose add 1U insulin) were transfused during operation. The levels of blood sugar and plasma insulin were measured before and after anesthesia, during operation(30min) and after operation respectively.Results There was an insulin resistance phenomenon in patients with obesity. The levels of blood sugar and plasma insulin in patients with obesity were remarkably higher than those in patients of normal weight. The levels of blood sugar and plasma insulin were extrenely raised after anesthesia and during operation. The levles of blood sugar was inhibited as insulin was infused during operation, bul no hypoglycemic reaction was found.Conclusion There are insulin resistance phenomenon in patients with obesity. Insulin infused during operation can prevent blood sugar rise and minimize glucose meta bolism turbulence.
    Comparative cardiotoxicity of propofol and thiopental in neonatal primary myocardial cell cultures
    ZHANG Tie-Zheng, WANG Feng-Xue, XIU Xiao-Jiang, WANG Chao-Ren
    1999, 4(4):  299-302. 
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    Aim To investigate the cardiotoxicity of propofol and thiopental. Methods 4 day-old contracting neonatal primary myocardial cells obtained from 2-to 3-day-old Wistar rats were divided into 5 groups,with normal contrast group, and the cell cultures in groups PL,PH, TL and TH, were treated with propofol(3x 10-5 and 3X 10-4 mol·L) and thiopental (1X 10-5 and 1X 10-4 mol·L) for 8 h. The contractility and morphology of the cells were observed and the cytoplasmic enzyme (LDH, AST, CK and ALP) release content of myocardial cell and the concentration of electrolytes (K+, Na+, Cl- and Ca2+) in the medium were measured 8 h after intravenous anesthetics administration.Results In group-PH and TL decreased significantly (P<0.05 and P<0.01) and the cells showed partly beating or no beating in group TH. The enzemy (LDH, AST and CK) release of the cell cultures in group TL,TH and PH was increased (P<0.05 and P<0.01) and ALP decreased, associateing with in adverse effect on morphology. The results show that group PL had litle or no effect on all indices of toxicity evaluated. Electrolytes were not significantly different, among all groups.Conclusion The low concentrations of thiopental and high concentrations of propofol have significant direct myocardial depressant action, especially the high concentrations of thiopental, while low concentrations of propofol has little or no effect on cardiotoxity.
    Immunopharmacological actions of capsule bushenyanshou in mice
    WANG Hui, CHEN Jin-He, KONG Rui, LI Qi-Xiong, KONG Rui
    1999, 4(4):  303-305. 
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    Aim The effect of capsule bushenyanshou (BSYS),a compound of traditional Chinese medicine,on the immunopharmacological activities of mice was investigated. Methods The indexes of immunopharmacological activity, such as the clearance rate of charcoal particles, the lymphocyte transformation and the content of serum hemolysin, were measured.Results Capsule BSYS (400, 800 mg·kg-1,qdX12) markedly increased the clearance rate of iv charcoal particles and the lymphocyte transformation stimulated in vivo by PHA in mice. In hydrocortisone-treated mice(15 mg·kg-1, scqdX 5),capsule.BSYS significantly enhanced the content of serum hemolysin and the weights of spleen and thymus. The results also demonstrated capsule BSYS performed a sighted inhibition of the delayed type hypersensitivity in mice.Conclusion Capsule BSYS has the capacity of immunological intensification and regulation.
    Effect of hemodialysis on pharmacokinetics of sparfloxacin in the patients with chronic renal failure
    LIANG Zhu, SHAO Rong-Zi, ZHANG Ying-Wei, ZHANG Ei-Ping, YUAN Chen
    1999, 4(4):  306-308. 
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    Aim To observe the effect of hemodialysis on pharmacokinetics of sparfloxacin in the patients contracting chronic renal failure. Methods Sparfloxacin concentrations in serum and urine of hemodialysis and non-dialysis patients were measured with a high performance liquid chromatography method after administration a single oral dose of 200 mg sparfloxacin. The pharmacokinetic parameters were computed with the program PKBP-N.Results The main pharmacokinetic parameters in hemodialysis group were T1/2(ka)= (1.25士0.57) h,T1/2(β)= (11.88士4.13) h,Tpeak = (4. 18士0.78) h, Cmax =(0.80+0.17) mg·L-1 and AUC0~∞= (6. 90土3.25) mg·h·L-1,while in non-dialysis group were T1/2(ka)= (1.12+0.42) h, T1/2(β)= (15.93土5.20) h, Tpeak =(3. 88土0.75) h, Cmax= (0. 69+0.37) mg·L-1, AUC0~∞= (10.05士4.13) mg·h·L-1. The original sparfloxacin discharge rats in urine within 24 h were (8. 98士3.92)% and (10. 58土5. 64) % separately. Tr2q) and AUC in hemodialysis group were markedly lower:than in non-dialysis group (P<0. 05).Conclusion The pharmacokinetics of sparfloxacin in patients contracting chronic renal failure is not changed by hemodialysis.
    Timed analgesic effects by butabital, acetaminophen and affeine in combination in mice and rats1
    YANG Hui-Jie, ZHENG Qing-Shan
    1999, 4(4):  309-312. 
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    Aim To observe the timed analgesic efets by butabital (B), acetaminophen (A) and affeine (C) in combination (BAC), in which the proportion was fixed as 1.25:8.1:1.Method Three types of experimental methods, including the tail flicking method, the hot plate method and the pessring tail method, were taken to detemine indices at diferent times after the animals were administered (ig) high, median and low BAC dose.Results and Conclusion BAC had a strong analgesic effect in three types of experiments. The effect began 30 min after administation, arived maximum at 1 bh, decreased al 2h and disppeared at 4h. There was a dose efet relationship between large and lite BAC dose.
    Clinical use of mycophenolate mofetil in renal taransplation
    DONG Ya-Lin, WANG Mao-Yi, HUANG Meng, TIAN Pu-Xun, PANG Sheng-Qiang
    1999, 4(4):  313-315. 
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    Aim To monitor the w hole blood trough concentration of cyclosporine A (CsA) in renal prednisone and to establish an optimal therapeutic window of CsA.Methods Samples were measured by specific fluorescence polarization immunoassay. According to the time after operation and different therapy plan, the whole blood trough concentration of CsA in each group was compared with that in control group.Results The optimal therapeutic window of CsA with MMF plan was 150~ 300 μg·L-1(less than one month after operation),120~ 260μg· L-1(1~<3 mon) and 100~ 225 μg·L-1(3 ~<6 mon).Conclusions The optimal therapeutic window of CsA with MMF plan are lower than control groups in the incidence of toxic effects and the rejection reaction is diminished obviously.
    Clinical efficacy of anti-hyperetnsive drug losartan in hypretensive patients with left ventricular hypertrophy
    JIANG Zhi-An, ZHANG Xiao-Guang, XIAO Wen-Liang, ZHAO Wei-Jiang
    1999, 4(4):  316-318. 
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    Aim The study is to observe the clinical efficacy of losartan in hypertentive patients with left ventricular hypertrophy. Methods 21 case were given losartan for 20 wk and 24 h ambulatory blood pressure monitoring and color doppler echocardiography were performed in the patients before and after treatment.Results The24hSBP,24hDBP,dDBP, nSBP were from (151土15)、 (93士9)、(155土15)、(96土10)、(146士16)、(88士11)mmHg before treatment to (132士11)、(82士8)、(137士12)、(88士9)、(120土9)、(120士15)、(74士9) mmHg after treatment respectively and the IVST, PWT and LVMI were from (14.2土1.5) mm、(13.9土1.45) mm、(152.1+24.2) g·m2-1 BSA before treatment to (12.1土1.31) mm、(12.2士1.41) mm、(130.6+23.1) g·m2-1 BSA after treatment respectively.. All the parameters after treatment in the patients were significantly decreased as compared with those before treatment (P<0. 01).Conclusion Losartan can significantly lower the blood pressure and the left ventricular hypertrophy in hypertensive patients with left ventricular hypertrophy.
    Effect of multiglycosides of tripyergium wilfordii (GTW) compound on female rat reproductive system
    LINAG Wen-Bo, DONG He-Yan, LENG Ping
    1999, 4(4):  319-321. 
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    Aim The side and toxic effects on reproductive system of female rat caused by compositus GTW were observed. Methods In three dosages (11.27 g·kg-1, 5.64.g·kg-1and2.82g·kg-1of each ary herbs), the 13 specified traditional Chinese medical herbs, including Trichosanthes Kirilowii, dendronium clavatum, Paeonia lactiflora,et al. were detected and concentrated to 10 ml·kg-1 decoctums. The decoctums were each mixed with 30 g·kg-1 GTW to compose the GTW compounds. GTW and GTW compounds, in the same dose, were given separetely to the rats in different groups for 80 days. Cytological examination was performed 10 days before finishing the experiment and changes of uterus and ovary were observed after the experiment.Results In the GTW group the ovulatory period was irregular, the weight of uterus was lost and its muscle became thinner, as compared with those in the control group, while in the GTW compound groups the toxic effects found in the GTW group were apparently redressed.Conclusion The side and toxic effects of GTW compound on reproductive system of female rats are apparently lower than those of GTW.
    Study of the antiuler effet of pantoprazole
    WANG Ying-Xin, LI Xiao-Qiang, WU Guang-Wu, Qian Shan-Jun, LEI Hong, CAO Chang
    1999, 4(4):  322-324. 
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    Aim To evaluate the effect of pantpraole on various xerimental acule ule in rats and mice. Methods The model of a gastric uler of rats or mice was caused by steinduced uler and ligatel pyluru-induced ulcer.I Results &Conclusions At a dose of 5, 10,20 mg·kg-1of Pantoprazole can markedly decrease the ulcer index of the area stree indued uler Panopraole(4, 8.16 mg·kg-1) sificanly derease of igted pylorusindued gatrice uler. It was also found that pnopraole can inhibit the output of basic gastric acid.
    Quantitative design of clinical scheme of combinatiou drug therapy1
    ZHENG Qing Shan
    1999, 4(4):  325-330. 
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    Aim To show the performance of the weighted modification method in the clinical design of combination drug therapy. Methods A scheme combined by Drug1, Drug2 and Drug3 was used to treat infants with iron deficiency anemia for 2 wk in a hypothetical clinical trial. Thirty-six infants were randomly into 6 compound groups. Three drugs in the scheme were divided into 6 dose levels, which were evenly distributed to the 6 groups according to the weighted modification method. The increased Hb (△Hb) was recorded at 2, 3, 4 wk after the treatment (po). The dose-effect data at 4 wk were analyzed by the method, and then the doses in scheme were modified by the analytic result. The modified doses in the scheme would be further demonstrated.Results Drug1 and Drug2 were principal drugs, but Drug1 had larger contribution to the combined effect (△Hb) than Drug2. Drug3 had lttle effect. There was a strong synergism between Drug1 and Drug2 with the weighted coefficient (b1) =2. 636(P<0.05), and a slight synergism between Drug2 and Drug3 with bz =0.460 (P<0. 05). But there was a significant antagonism between Drug1 and Drug3 with the weighted cofficient(B) =-0.829 (P<0.05) 。The doses were adjusted to form a new scheme with Drug1 60 mg·kg-1 +Drug2 10 mg·kg-1(p) and Drug 3 was deleted from the scheme. The scheme was an optimal one confirmed by a demonstration trial.Conclusion This method is able to effectively determine important degree of drugs in combination, and to optimize their doses for designing the scheme of combination drug therapy.