Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1...Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.展开更多
[ Objective ] The insecticidal and antibacterial bioactivity of Wikstroemia chamaedaphne Meissn were screened and bioactive substances in it were separated and purified. [ Method] The Wikstroemia chamaedaphne Meissn w...[ Objective ] The insecticidal and antibacterial bioactivity of Wikstroemia chamaedaphne Meissn were screened and bioactive substances in it were separated and purified. [ Method] The Wikstroemia chamaedaphne Meissn was conducted ultrasonic extraction in petroleum ether, ethyl acetate and methanol. The insecticidal activity of Wikstroemia chamaedaphne Meissn to Mythimna separata walker and aphid were determined. The antibacterial activity of Wikstroemia chamaedaphne Meissn to Fusarium graminearu, Glomerella cingulata, F. oxysporium f. sp niveum, Alternaria solani and Fusarium oxysporium were also determined. The bioactivity-guided methods such as opencolumn chromatography and Pre-HPLC method were used to separate active components in petroleum ether extract from Wikstroemia chamaedaphne Meissn. [ Result] When the concentration was 500 mg/L, 3 kinds of extracts from Wikstroemia chamaedaphne Meissn didn＇ t show obvious antibacterial bioactivity to 5 kinds of test samples. When the concentration was 5%, petroleum ether extract show certain topical toxicity to aphids. The ethyl acetate extract showed certain antifeedant activity to 3^rd instar Larvae of Mythimna separata Walker. The fraction F4 of petroleum ether extract possessed highest topical toxicity to aphids and the lethality was 60.00%. [ Conclusion] Wikstroemia chamaedaphne Meissn contained many insecticidal constituents whose active parts and mechanism were needed further researches.展开更多
Objective： To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m^2 gemcitabine using standard 30-min infusion or fixed dose rate （FDR） infusion [10 mg...Objective： To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m^2 gemcitabine using standard 30-min infusion or fixed dose rate （FDR） infusion [10 mg/（m^2-min）] on days 1 and 8 plus carboplatin AUC （area under curve） 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study. Methods： Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria. Results： The obtained mean parameters, such as T1/2 （elimination half time）, AUC, and CL （clearance）, were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR ann. Additional 50% and 33.3% patients contracted stable disease （SD） in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion ann experienced consistently more hematologic toxicity, Conclusion： Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.展开更多
The interactions among drugs,tumor and host are critical for a response to therapy and for outcome.Anticancer herbs used in Chinese medicine are classified into 4 groups based on their target (tumor,patient and drug) ...The interactions among drugs,tumor and host are critical for a response to therapy and for outcome.Anticancer herbs used in Chinese medicine are classified into 4 groups based on their target (tumor,patient and drug) as follows:eliminating pathogenic factors,strengthening the body resistance,enhancing effects of chemotherapy and detoxication of chemotherapy. Correspondingly,anticancer drugs used in Western medicine can be classified into 4 groups as follows:cytotoxic drugs,biological response modifiers,chemosensitizers and chemoprotectants. Based on the theory of Chinese medicinal formulas,prescriptions are composed of four constituents,namely,primary constituent (main component of the formula prescription),minister constituent (second component of formula prescription),adjuvant constituent (adjuvant component of the formula prescription) and messenger constituent (component making the formula prescription targeting pathological tissues).To control the interaction among drugs and to modulate the interaction among the tumor,patient and drugs,we suggest that combined therapy for Western medicine might include 4 constituents,i.e.,primary,cooperative,adjuvant and modulatory constituent. Cytotoxic drugs frequently are used as primary and cooperative constituents,whereas biological response modifiers and biochemical modulators are usually regarded respectively as adjuvant drugs and modulatory constituents. We believe these new concepts may be helpful for the aim of appropriately designing,evaluating or providing combination therapy.展开更多
Feeling peaky？Let＇s learn some words on medicine in Chinese.Compared to西医（xi yi）,Western medicine,中医（zhong yi）,traditional Chinese medicine（TCM）,and Chinese herbs seem a little bit mysterious.The character...Feeling peaky？Let＇s learn some words on medicine in Chinese.Compared to西医（xi yi）,Western medicine,中医（zhong yi）,traditional Chinese medicine（TCM）,and Chinese herbs seem a little bit mysterious.The character for＂medicine＂in Chinese has a radical which means herb,probably because药草（yao cao）,Chinese medicinal herbs,are the fundamental elements of中药学（zhong yao xue）.展开更多
A sensitive RP-HPLC-UV method has been developed and validated for the quantification of daphnoretin in rat plasma. Daphnoretin was extracted from rat plasma by protein precipitation and liquid-liquid extraction. Sepa...A sensitive RP-HPLC-UV method has been developed and validated for the quantification of daphnoretin in rat plasma. Daphnoretin was extracted from rat plasma by protein precipitation and liquid-liquid extraction. Separation was performed on a Diamonsil C18 column （200 mm× 4.6 mm, 5 μm） with a mobile phase of methanol-20 mmol/L ammonium acetate （adjusted to pH 3.2 with acetic acid, 42：58, v/v） at a flow rate of 1.0 mL/min. The UV detector was set at 345 nm and column temperature was set at 40 ℃. The calibration curves were linear over the concentration range of 0.020-2.00 ~tg/mL, The lower limit of quantification （LLOQ） of daphnoretin in rat plasma was 0.020 μg/mL. The intra- and inter-day relative standard deviation （RSD） for measurement of quality control （QC） samples （0.050, 0.200 and 1.60 μg/mL） ranged from 5.0%-10.6%. Relative error （RE） was from ±（1.2%-2.5%）. The validated method was used successfully in a pharmacokinetic study of daphnoretin in rats after intraperitoneal injection.展开更多
In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite（CAM）. Th...In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite（CAM）. The traditional Chinese medicines（TCMs） Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule are widely used to treat cardiovascular disease in China. They are often prescribed in combination with clopidogrel, a common anti-platelet Western drug. We investigated the influence of the four TCMs on CAM pharmacokinetics following administration at human dose in rats. Pharmacokinetic parameters were determined following oral（PO） administration of clopidogrel（7.5 mg/kg） with or without Rong Shuan capsule（75 mg/kg, PO）, Xue Zhi Kang capsule（60 mg/kg, PO）, Xin Yuan capsule（120 mg/kg, PO）, or Songling Xue Mai Kang capsule（150 mg/kg, PO）. Compared with the animals in the control group, Xue Zhi Kang capsule significantly decreased the area under the plasma concentration-time curve（AUC_（0-t）） of the CAM derivative by 25.4%. However, the t1/2 and Vz/F of CAM derivative were significantly increased by 43.6% and 70.7%, respectively. It was also observed that the pharmacokinetic parameters were altered in groups pretreated with Rong shuan capsule, Xin yuan capsule or Songling Xue mai kang capsule compared with the control group, but not significant. This study indicated that Xue Zhi Kang capsule had an effect on the formation and metabolism of CAM. Therefore, in the beginning of co-administration of Xue Zhi Kang capsule and clopidogrel, the anti-platelet efficacy might be compromised because of the decreased formation of CAM. Otherwise, long-time co-administration might lead to side effects by the prolongation of the t1/2 and Vz/F increase of CAM.展开更多
OBJECTIVE: To compare the effects of integrated Chinese-Western therapy versus Western therapy alone on the survival rate of patients with non-small-cell lung cancer (NSCLC) at middle-late stage and to evaluate progno...OBJECTIVE: To compare the effects of integrated Chinese-Western therapy versus Western therapy alone on the survival rate of patients with non-small-cell lung cancer (NSCLC) at middle-late stage and to evaluate prognostic factors. METHODS: We selected 98 inpatients with middle-late stage NSCLC diagnosed from March 2009 to March 2011 and randomly divided them into two groups, with 49 cases in each group, and the clinical data were analyzed retrospectively.The control group was treated by the combined methods of Western Medicine, including chemotherapy, supportive treatment and symptomatic treatment. The observation group was treated by injection and prescriptions of Chinese medicine based on Traditional Chinese Medicine syndrome differentiation and by the same combined methods of western treatment used in the control group. After treatment, the survival rates of the patients were compared by the stage of cancer and evaluation of 24 prognostic factors analyzed by a Cox regressionmodel, and the clinical data were statistically analyzed. RESULTS: The survival rates of all patients were over 90.0% at 1 and 3 months after treatment with no significant differences between the two groups (P>0.05); In the observation group the survival rates at 6 months and 1 year were 93.4% and 42.8%, respectively, being superior to 85.6% and 18.3% in the control group (P<0.05). The median survival time in the observation group was superior to the control group (P<0.05); The effects of 24 prognostic factors were significantly better in the observation group than in the control group (P<0.05). CONCLUSION: Integrated Chinese-western therapy can significantly improve the survival rate in patients with middle-late stage NSCLC and improve prognostic factors compared with western therapy alone.展开更多
文摘Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.
基金Supported by School Project of Yan’an University (YD2005-042)~~
文摘[ Objective ] The insecticidal and antibacterial bioactivity of Wikstroemia chamaedaphne Meissn were screened and bioactive substances in it were separated and purified. [ Method] The Wikstroemia chamaedaphne Meissn was conducted ultrasonic extraction in petroleum ether, ethyl acetate and methanol. The insecticidal activity of Wikstroemia chamaedaphne Meissn to Mythimna separata walker and aphid were determined. The antibacterial activity of Wikstroemia chamaedaphne Meissn to Fusarium graminearu, Glomerella cingulata, F. oxysporium f. sp niveum, Alternaria solani and Fusarium oxysporium were also determined. The bioactivity-guided methods such as opencolumn chromatography and Pre-HPLC method were used to separate active components in petroleum ether extract from Wikstroemia chamaedaphne Meissn. [ Result] When the concentration was 500 mg/L, 3 kinds of extracts from Wikstroemia chamaedaphne Meissn didn＇ t show obvious antibacterial bioactivity to 5 kinds of test samples. When the concentration was 5%, petroleum ether extract show certain topical toxicity to aphids. The ethyl acetate extract showed certain antifeedant activity to 3^rd instar Larvae of Mythimna separata Walker. The fraction F4 of petroleum ether extract possessed highest topical toxicity to aphids and the lethality was 60.00%. [ Conclusion] Wikstroemia chamaedaphne Meissn contained many insecticidal constituents whose active parts and mechanism were needed further researches.
基金Project (No.2004A028) supported by the Medical Science Research Foundation of Zhejiang Province,China
文摘Objective： To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m^2 gemcitabine using standard 30-min infusion or fixed dose rate （FDR） infusion [10 mg/（m^2-min）] on days 1 and 8 plus carboplatin AUC （area under curve） 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study. Methods： Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria. Results： The obtained mean parameters, such as T1/2 （elimination half time）, AUC, and CL （clearance）, were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR ann. Additional 50% and 33.3% patients contracted stable disease （SD） in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion ann experienced consistently more hematologic toxicity, Conclusion： Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.
文摘The interactions among drugs,tumor and host are critical for a response to therapy and for outcome.Anticancer herbs used in Chinese medicine are classified into 4 groups based on their target (tumor,patient and drug) as follows:eliminating pathogenic factors,strengthening the body resistance,enhancing effects of chemotherapy and detoxication of chemotherapy. Correspondingly,anticancer drugs used in Western medicine can be classified into 4 groups as follows:cytotoxic drugs,biological response modifiers,chemosensitizers and chemoprotectants. Based on the theory of Chinese medicinal formulas,prescriptions are composed of four constituents,namely,primary constituent (main component of the formula prescription),minister constituent (second component of formula prescription),adjuvant constituent (adjuvant component of the formula prescription) and messenger constituent (component making the formula prescription targeting pathological tissues).To control the interaction among drugs and to modulate the interaction among the tumor,patient and drugs,we suggest that combined therapy for Western medicine might include 4 constituents,i.e.,primary,cooperative,adjuvant and modulatory constituent. Cytotoxic drugs frequently are used as primary and cooperative constituents,whereas biological response modifiers and biochemical modulators are usually regarded respectively as adjuvant drugs and modulatory constituents. We believe these new concepts may be helpful for the aim of appropriately designing,evaluating or providing combination therapy.
文摘Feeling peaky？Let＇s learn some words on medicine in Chinese.Compared to西医（xi yi）,Western medicine,中医（zhong yi）,traditional Chinese medicine（TCM）,and Chinese herbs seem a little bit mysterious.The character for＂medicine＂in Chinese has a radical which means herb,probably because药草（yao cao）,Chinese medicinal herbs,are the fundamental elements of中药学（zhong yao xue）.
基金National Key Scientific Project for New Drug Discovery and Development(Grant No.2009ZX09301-012)
文摘A sensitive RP-HPLC-UV method has been developed and validated for the quantification of daphnoretin in rat plasma. Daphnoretin was extracted from rat plasma by protein precipitation and liquid-liquid extraction. Separation was performed on a Diamonsil C18 column （200 mm× 4.6 mm, 5 μm） with a mobile phase of methanol-20 mmol/L ammonium acetate （adjusted to pH 3.2 with acetic acid, 42：58, v/v） at a flow rate of 1.0 mL/min. The UV detector was set at 345 nm and column temperature was set at 40 ℃. The calibration curves were linear over the concentration range of 0.020-2.00 ~tg/mL, The lower limit of quantification （LLOQ） of daphnoretin in rat plasma was 0.020 μg/mL. The intra- and inter-day relative standard deviation （RSD） for measurement of quality control （QC） samples （0.050, 0.200 and 1.60 μg/mL） ranged from 5.0%-10.6%. Relative error （RE） was from ±（1.2%-2.5%）. The validated method was used successfully in a pharmacokinetic study of daphnoretin in rats after intraperitoneal injection.
基金Foundation of Science and Technology Department of Hebei Province(Grant No.14277747D)
文摘In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite（CAM）. The traditional Chinese medicines（TCMs） Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule are widely used to treat cardiovascular disease in China. They are often prescribed in combination with clopidogrel, a common anti-platelet Western drug. We investigated the influence of the four TCMs on CAM pharmacokinetics following administration at human dose in rats. Pharmacokinetic parameters were determined following oral（PO） administration of clopidogrel（7.5 mg/kg） with or without Rong Shuan capsule（75 mg/kg, PO）, Xue Zhi Kang capsule（60 mg/kg, PO）, Xin Yuan capsule（120 mg/kg, PO）, or Songling Xue Mai Kang capsule（150 mg/kg, PO）. Compared with the animals in the control group, Xue Zhi Kang capsule significantly decreased the area under the plasma concentration-time curve（AUC_（0-t）） of the CAM derivative by 25.4%. However, the t1/2 and Vz/F of CAM derivative were significantly increased by 43.6% and 70.7%, respectively. It was also observed that the pharmacokinetic parameters were altered in groups pretreated with Rong shuan capsule, Xin yuan capsule or Songling Xue mai kang capsule compared with the control group, but not significant. This study indicated that Xue Zhi Kang capsule had an effect on the formation and metabolism of CAM. Therefore, in the beginning of co-administration of Xue Zhi Kang capsule and clopidogrel, the anti-platelet efficacy might be compromised because of the decreased formation of CAM. Otherwise, long-time co-administration might lead to side effects by the prolongation of the t1/2 and Vz/F increase of CAM.
文摘OBJECTIVE: To compare the effects of integrated Chinese-Western therapy versus Western therapy alone on the survival rate of patients with non-small-cell lung cancer (NSCLC) at middle-late stage and to evaluate prognostic factors. METHODS: We selected 98 inpatients with middle-late stage NSCLC diagnosed from March 2009 to March 2011 and randomly divided them into two groups, with 49 cases in each group, and the clinical data were analyzed retrospectively.The control group was treated by the combined methods of Western Medicine, including chemotherapy, supportive treatment and symptomatic treatment. The observation group was treated by injection and prescriptions of Chinese medicine based on Traditional Chinese Medicine syndrome differentiation and by the same combined methods of western treatment used in the control group. After treatment, the survival rates of the patients were compared by the stage of cancer and evaluation of 24 prognostic factors analyzed by a Cox regressionmodel, and the clinical data were statistically analyzed. RESULTS: The survival rates of all patients were over 90.0% at 1 and 3 months after treatment with no significant differences between the two groups (P>0.05); In the observation group the survival rates at 6 months and 1 year were 93.4% and 42.8%, respectively, being superior to 85.6% and 18.3% in the control group (P<0.05). The median survival time in the observation group was superior to the control group (P<0.05); The effects of 24 prognostic factors were significantly better in the observation group than in the control group (P<0.05). CONCLUSION: Integrated Chinese-western therapy can significantly improve the survival rate in patients with middle-late stage NSCLC and improve prognostic factors compared with western therapy alone.
