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

Table of Content

    Volume 2 Issue 4
    26 December 1997
    Effects of nerve growth factor on intracellular free Ca2+ in isolated brain cells of neonatal rat
    Wu Junfang, Zhang Juntian
    1997, 2(4):  241-244. 
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    Aim Effects of nerve growth factor (NGF) on intracellular free Ca2+ concentration ([Ca2+ ]i) in isolated brain cells of neonatal rat were observed. Methods [Ca2+ ]i was measured with Ca2+ sensitive fluorescent indicator, Fura-2/AM, in isolated brain cells of neonatal rat, and the effects of nerve growth factor (NGF)on the changes in [Ca2+ ]i induced by glutamate (Glu)and hydrogen perioxide (H2O2)were studied. Results The resting [Ca2+ ]i was 208 ±22 nmol/L when the brain cells were incubated in Hanks'solution containing Ca2+ 1.3nmol/L. NGF did not alter the resting [Ca2+ ]i in brain cells.NGF 1~ 100 μg/L dose-dependently attenuated glutamate (0.5 mmol/L)and hydrogen peroxide (0.05 mmol/L)induced elevation of [Ca2+ ]i by 10%, 18%, 32%, 44%, 62%and 14%, 30%, 39%, 49%, and 65%, respectively, with an IC50 of 42.5 and 27.3μg/L (95%confidence limits:28.1~ 71.5 and 18.1~ 46.5 μg/L).Conclusion These suggest that NGF protect cortical neurons against glutamate toxicity and oxidative in-sults via reducing the elevation of [Ca2+ ]i or stabilizing [Ca2+ ]i level.
    Vitamin E protects function of remnant kidney
    Yuan Fahuan, Shi Jingquan, Guang Lixia, Liao Lisheng
    1997, 2(4):  245-248. 
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    Aim To investigate whether vitamin E could protect the function of remnant kidney in chronic renal failure (CRF)rats.Methods The 120 adult male Wistar rats were divided into 3 groups. Rats in group A received a sham operation serving as the negative control. Rats in group B were given a 5/6 nephrectomy serving as the positive control. Rats in group C were operated as the rats in group B and received treatment of vitamin E in their chow. The renal function and oxygen free radical metabolism of every group were assayed with the biochemical methods 30, 60, 90, 120 days after the operation. Results In group B, there were a marked increase of plasma creatinine, urea concentration, urine protein concentration, mean arterial blood pressure, and renal tissue lipid peroxide concentration, and a significant decrease of hemoglobin content, hematocrit, re-nal tissue vitamin E content, renal tissue superoxide dismutase and catalase activity, as com-pared with those in group A. In group C accompanied with the decrease of renal lipid peroxide, and increase of renal vitamin E content, tenal superoxide dismutase and catalase activity, all the indices of renal function became better than those is group B. Conclusion Vitamin E could protect the function of remnant kidney in 5/6 nephrectomy induced CRF rats, which might due to its antioxidant roles.
    Effect of food on bioavailability of cinnarizine capsules
    Wei Guangli, Xiao Shuhua, Liu Changxiao
    1997, 2(4):  249-252. 
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    Aim To compare the effectsof food on the bioavailability of two kinds of cinnarizine capsules (A and B). Methods HPLC method with UV detection was used to measure the serum cinnarizine concentration in 12 healthy human volunteers after a single 50mg oral dose both in fasting condition and with a meal. Results The peak plasma concentration (Cmax)and the area under the plasma concentration time curve (AUC)of capsule A appeared to be unchanged in the presence of food, but food significantly affected the extent of absorption of capsule B. The Cmax and AUC of capsule B in fasting condition were significantly less than those with a meal. Conclusion The formulation of capsule A had advantage over capsule B. Its bioavailability was not affected by food.
    Effects of propofol and ketamine on Na+, K+-ATPase activity of synaptosomes in rat brain in vivo
    Hu Xingguo, Wang Jun, Zeng Yinming, Duan Shiming, Dai Tijun, Xu Pengcheng, Wan Lingli
    1997, 2(4):  253-255. 
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    Aim To investigate the effects of propofol and ketamine on Na+, K+-ATPase activity in rat brain synaptosomes.Methods Thirty SD rats were divided randomly into three groups. The aminals were given intraperitoneally (ip)normal saline 10ml/kg (control group), propofol 100mg/kg or ketamine 100mg/kg, respectively. Na+, K+-ATPase activity of synaptosmes was assassed by spectrophotometric analysis.Results In the propofol group Na+, K+-ATPase activities of cerebrocortical, hippocampal and brain stem synaptosomes were significantly inhibited as compared with those in the control group (P<0.01). In the ke-tamine group, Na+, K+-ATPase activities of cerebrocortical and brain stem synaptosomes were significantly lower than those in the control group (P<0.01). Conclusions The general anesthesia effects of propofol and ketamine may be related to the inhibition of Na+, K+-ATPase activity of brain synaptosomes in rats.
    Monitoring of whole blood level of cyclosporine in 3275 samples from 521 renal transplant recipients by specific fluorescence polarization immunoassay
    Xia Dongya, Zhao Qingchun, Liu Baoqing, Xiang Jun, Liu Long, Wu Qiusheng
    1997, 2(4):  256-259. 
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    Aim To monitor the whole blood trough concentration of cyclosporine A(CsA)in renal transplant recipients, and to suggest optimal therapeutic window of CsA. Methods CsA concentration in 3275 blood samples from 521 renal transplant recipients was measured by specific fluorescence polarization immunoassay. The whole blood trough CsA concentrations were compared according to different times after operation and clinical symptoms.Results The optimal therapeutic window of CsA should be 250~ 450 μg/L (less than 1 month after operation), 200~ 400 μg/L(1~ 3 months), 150~ 300 μg/L (3~ 6 months), 100~ 250 μg/L (6~ 12 months), 100~ 200 μ g/L(1~ 2 years), 100~ 180 μ g/L(more than 2 years), 100~ 180 μg/L(more than 2 years), respectivily. Conclusion The satistical analysis indicated that frequency of toxic effects and rejection reaction would significantly be reduced if CsA whole blood levels were adjusted to therapeutic and safe range.
    Effects of anticarcinogents on ondansetron pharmacokinetics in primary lung carcinoma patients
    Yuan Cheng, Wang Jingxiang, Liu Shuying, Li Xiaohua
    1997, 2(4):  260-263. 
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    Aim To research the effects of anticarcinogens on the pharmacokinetics of on-dansetron. Methods The pharmacokinetics of ondansetron was studied in 21 cases of primary lung carcinoma treated with methotrexate, 5-fluorouracil, lomustine, cyclophosphamide plus vincristine, and cis-platin. Before and within chemotherapy, ondansetron concentrations in plasma were determined by a reversed-phase high performance liquid chromatography. The data obtained were fitted with PKBP-N1 pharmacokinetic program. Results The plasma drug concentration-time course conformed to a two-compartment open model with a rapid absorption both before and after chemotherapy. Because methotrexate and lomustine were taken in single/large dose schedule, they did not cause the pharmacokinetic parameters of ondansetron to change markedly, but T1/2β was prolonged for about 0.5h. Other three chemother apiescaused the parametersof ondansetron to changemarkedly, except T1/2ka and Tmax, T1/2β was prolonged for 1h T1/2α hada irregular change, and Cmax and AUC were remarkably increased.But ondansetronwas stored up in patient's body after taken with multi-dose.Conclusion The test points out that regulating rationaly medicine plan is necessary when ondansetron is used within sustained chemotherapy.
    Establishment and application of imitative system adsorption chromatography
    Yu Huixing, Cao Guoxian, Huang Xuquan
    1997, 2(4):  264-266. 
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    Aim An imitative system of adsorption chromatography was established and applied.Methods A multi-compartment desorption theory model in adsorption-chromatography was put for-ward, some formulae were deduced and a computer program was compiled. Results The model could imitate the best curve of adsorption-chromatography according to the experimental re-quirement and reveal the relationship between the time and the concentration of a certain com-partment. Conclusion The system could bring about a better isolation effect than the tradi-tional method of two-compartment linear desorption.
    Effects of prazosin hydrochloride on rabbits plasma digoxin levels
    Zhang Zhiping, Chen Qian, Guo Guirong, Chen Yihong
    1997, 2(4):  267-269. 
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    Aim To study the influence of prazosin hydrochloride on plasma digoxin levels when pra-zosin hydrochloride was added after administration of single dose or multiple doses of digoxin. Methods After po 20 μg/kg of digoxin with or without addition 150 μg/kg of prazosin hy-drochoride, the rabbit plasma digoxin levels were monitored by TDX.T-test was used to e-valuate the difference between the plasma digoxin levels after prazosin hydrochloride was added or not. Results The absorption course and elimination course of digoxin were prolonged when single dose of digoxin was given, and after multiple doses of digoxin, the steady state concentrations of digoxin were significantly raised when single dose of prazosin hydrochloride was given 6h later. Conclusion The plasma digoxin levels should be adjusted individually for the patients who use digoxin combined with prazosin chronically.
    The clinical significance of detecting tumor necrosis factor and blood concentration of cyclosporin A and in renal transplanted recipients
    Sun Chengchun, Hao Junwen, Li Xiangtie, Wang jingxiang, Zhao jingyi
    1997, 2(4):  270-272. 
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    Aim To evaluate the clinical significance of determination of serum or urine tumor necrosis factos (TNF)and whole blood concentration of cyclosporin A (CsA)in renal transplanted recipients.Methods The serum and urine TNF levels with radioimmunoassay and whole blood concentration of CsA with FIPA method were determined in 55 renal transplanted re-cipients.Results Serum and urine TNF levels in group of acute rejection (1.03±0.26 ng/ L, 0.44±0.36 ng/L)were significantly higher than those in group of functionally stable re-nal graft(0.86±0.21ng/L, 0.34±0.29 ng/L)and there was an obvious elevation of the TNF as early as 1~ 3 daysbefore the rise of serum creatine.But the TNF levels in CsA nephrotoxicity group (0.91±0.22 ng/L, 0.4±0.27 ng/L)were not significantly different from those in func-tionally stable renal graft group. The blood concentration of CsA was decreased in group of acute rejection and increased in group of CsA nephrotoxicity. Conclusion Determining TNF and CsA could distinguished the graft rejection from CsA nephrotoxocity. It has important clinical sig-nificance for regulation of the dosage of CsA.
    Effects of Zhuanggushenbao on hyperlipoidemia in mice
    Yang Yan, Wu Tie, Ai Chunmei, He Kang, Cui Liao
    1997, 2(4):  273-275. 
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    Aim The action of lowing serum lipid of Zhuanggushenbao, which was prepared from Epimedium, Astragalus Land Atractylodes, was observed.Methods Mouse hypercholes-terolemia model by injecting yolk and mouse hyperlipoidemia model by fedding high lipid foods were set up.The effects of Zhuanggushenbao in its low, medium and high dose on serum total cholesterol (TC), triglyceride (TG)and high density lipoprotein-chlesterol (HDL-ch)were studied. Results Medium and high dose Zhuanggushenbao could reduce serum TC (P <0.05), and increase HDL-ch obviously (P <0.01).But it could not affect serum TG nearly. Conclusion Zhuanggushenbao has a dose-effect relationship on lowing blood lipid.
    Relative bioavailability of acyclovir tablets
    Wang Keshen, Shao Qingxiang, Zhang Meiyun, Yang Hua, Sang Guowei
    1997, 2(4):  276-278. 
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    Aim To evaluate the relative bioavailability of two kinds of acyclovir tablets manufactured by Xian Ju or Li Zhu pharmaceutical company. Methods Nine normal volunteers were included in a two-way cross-over study design. Blood samples were taken after a single oral dose ad-ministration of acyclovir tablets of 400mg and serum acyclovir concentration was determined by HPLC. Results The mean values of bioavailability parameters for Xian Ju product were: T =1.6h, AUC=3.496 μg/ml·h, Cmax =1.011 μg/ml, MRT =3.27 h, respectively. For Li Zhu products, the parameters were:T =1.7h, AUC =3.693 μg/ml·h, Cmax =0.997 μg/ml, MRT = 3.53h. Conclusion The two one-sided tests showed that two kinds of acyclovir tablets were bioequivalent.