Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil （5-FU） in patients with advanced breast cancer. Methods Twenty...Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil （5-FU） in patients with advanced breast cancer. Methods Twenty-seven patients with breast cancer received repeated doses of 1 255 mg·m^-2 of capecitabine twice daily for 7 d. Blood, tumor, and adjacent healthy tissue samples were collected. The concentrations of capecitabine and its metabolite 5-FU were determined by HPLC. The concentration-time profiles of capecitabine and 5-FU were fitted by pharmacokinetic model. The tissue distribution factors for capecitabine and 5-FU, and the AUC ratios of 5-FU to capecitabine in plasma, tumor or adjacent healthy tissue, were calculated with pharmacokinetic parameters, respectively. Results The Ka of capecitabine was 1.17 h^-1 in plasma, 0. 46 h^-1 in tumor tissue, and 0. 61 h^-1 in healthy tissue. The AUCs of capecitabine were 2. 557 1 μg·mL^-1 ·h, 1. 629 2 μg·g^-1·h and 2. 085 0 μg·g^-1· h, and T1/2 was 0. 782 3 h, 1. 528 1 h and 1. 289 6 h in plasma, tumor, and healthy tissue, respectively. The AUCs of 5-FU were 0.418 7 μg·mL^-1 h, 1.671 7 μg·g^-1·h and 1.020 8 μg·g^-1·h; the T1/2 was 0. 631 3 h ,1.204 1 h and 1.031 2 h in plasma, tumor, and healthy tissue, respectively. The tissue distribution factors of capecitabine were 0. 637 1 in tumor （AUCcap-Tumor/AUCcap-plasma） and 0. 851 4 in healthy tissue （AUCcap-HT/AUCcap-plasma . The tissue distribution factors of 5-FU were 3. 992 6 in tumor （AUC5-FU-Tumor/AUC5-FU-plasma） and 2. 438 0 in healthy tissue （AUC5-FU-HT/AUC5-FU-plasma）. The AUC ratios of 5-FU to capecitabine were 0. 1637, 1. 0261, and 0. 489 5 in plasma, tumor, and healthy tissue, respectively. Conclusion The simulation curves for the disposition of capecitabine and its metabolite 5-FU in plasma and tissue basically describe the activation process of capecitabine metabolizing to 5-FU and 5-FU elimination. There are similar distributions for capecitabine in plasma, tumor, and healthy tissue. The exposure of 5-FU in tumor was found to be 3. 992 6 times greater than that in plasma and 2. 438 0 times greater than that in healthy tissue. Capecitabine may metabolize preferentially to 5- FU in tumor tissue after oral administration.展开更多
Myocyte enhancer factor 2B （MEF2B） gene belongs to myocyte enhancer factor 2 （MEF2） gene family. They are all widely expressed in muscle and nerve tissues of human and animals. MEF2B plays an important role in the...Myocyte enhancer factor 2B （MEF2B） gene belongs to myocyte enhancer factor 2 （MEF2） gene family. They are all widely expressed in muscle and nerve tissues of human and animals. MEF2B plays an important role in the growth of muscle, development and differentiation of nerve system and liver fibrosis. This re- view mainly focused on the structural characteristics, tissue distribution, biological functions and research progress of MEF2B gene in human and animals.展开更多
The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and uri...The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.展开更多
The author will propose that qualia--typically understood as the purely subjective and phenomenal elements of experience--are not specifically brain processes, but are instead best thought of as world processes that c...The author will propose that qualia--typically understood as the purely subjective and phenomenal elements of experience--are not specifically brain processes, but are instead best thought of as world processes that can be characterized as distributed self-organizing networks of Whiteheadian actual entities. If this is correct, then we need not wrestle with the materialist＇s ＂hard problem＂ of explaining how consciousness can arise from the purely objective particles and forces of fundamental ptiysics, but we will need to explain in what sense microparticles and other physical objects are experiential and objectively real without embracing panpsychism. Since Whiteheadian actual entities have intrinsic natures grounding the subjective and phenomenal aspects of experience, and extrinsic relations grounding objective physical properties, we find that qualia, understood in light of Whiteheadian actual entities, can provide the metaphysical foundations for both the subjective and objective aspects of the world.展开更多
An HPLC method for the determination of isovitexin in rat plasma and different tissues was developed.The separation was achieved on a C_（18）column with a mobile phase consisting of methanol-1% acetum（40：60,v/v）at...An HPLC method for the determination of isovitexin in rat plasma and different tissues was developed.The separation was achieved on a C_（18）column with a mobile phase consisting of methanol-1% acetum（40：60,v/v）at a detection wavelength of 338 nm and a column temperature of 30℃.Rutin was chosen as the internal standard.The linear range of the standard curves was 0.20-128.75μg/mL in the plasma and 0.024-3.09μg/mL in the tissues.The LOQ was 0.19μg/mL in the plasma and 0.024μg/mL in the tissues.The relative recoveries of isovitexin ranged from 93% to 105% in the plasma and 87% to 112% in the tissues.The intra-and inter-day precisions were all below 8%.The pharmacokinetics and tissue distribution of isovitexin in rats were studied with the method.Blood samples were collected at fixed time intervals after the i.v.injection of isovitexin at a dosage of 18.75,3.75 and 0.75 mg/kg;the tissue samples（brain,liver,kidney,heart,lung,spleen and ovary）were obtained at 10,30,and 60 min after the i.v.injection of isovitexin at a dosage of 18.75 mg/kg.The pharmacokinetics of the isovitexin in three different dosages in the rats fit the two-compartment open model.The isovitexin displayed linear dynamics in the dosage range of 0.75-18.75 mg/kg.The mean value of t_（1/2α）was 1.54-1.84 min,and t_（1/2β）was 36.94-46.27 min at the three dosages.The tissue distribution study showed that the sequence of tissue drug concentration from high to low was kidneyliverlung≈ovaryheart≈spleenbrain.展开更多
Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tiss...Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.展开更多
Brucine has anti-inflammatory and analgesic effects and is the main active compound of the seeds of Strychnos nux-vomica L. To study brucine niosomal gels, a reliable and rapid LC-MS/MS method was established to quant...Brucine has anti-inflammatory and analgesic effects and is the main active compound of the seeds of Strychnos nux-vomica L. To study brucine niosomal gels, a reliable and rapid LC-MS/MS method was established to quantify brucine levels in rats. Tissue distribution and pharmacokinetics of brucine were investigated after topical and oral application of brucine niosomal gels to rats. The plasma concentration versus time profiles suggested that systemic exposure of brucine for oral administration of brucine niosomal gels was higher than that for topical administration, and topical administration showed a relatively sustained release. There was a considerable amount of brucine distributed in the knee joint. These results provided a strong basis for the follow-up study of this preparation.展开更多
As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root ofStephania tetrandra S. Moore, tetrandrine （Tet） is widely used for the treatment of malignant tumor due to its properties of reversing...As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root ofStephania tetrandra S. Moore, tetrandrine （Tet） is widely used for the treatment of malignant tumor due to its properties of reversing the multidrug resistance and apoptosis induction. In the present study, we aimed to evaluate the pharmacokinetics, tissue distribution and excretion of Tet in rats. Drug concentration in plasma and tissues was measured by high performance liquid chromatography （HPLC）, and the experimental data were analyzed using pharmacokinetic software DAS 2.0. The results showed that the plasma protein binding rate of Tet was 68.7%, indicating a higher protein binding drug. Tissue distribution was found in a descending order as follows： lung〉heart〉liver〉kidney〉spleen. Renal excretion was a major route of excretion, and the urine, bile and fecal excretion accounted for 25.73% of the administered dose. A UC0-∞ of Tet in the liver was 20 times greater than that in plasma, indicating that Tet had a higher affinity for the liver. Moreover, CL in the liver was the lowest among all tissues, indicating that Tet with slow elimination might result in the accumulation. Therefore, we need to adjust the dose for patients who have dysfunction in liver and kidney. In addition, therapeutic drug monitoring in long-term clinical treatment, if necessary, should be carried out.展开更多
文摘Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil （5-FU） in patients with advanced breast cancer. Methods Twenty-seven patients with breast cancer received repeated doses of 1 255 mg·m^-2 of capecitabine twice daily for 7 d. Blood, tumor, and adjacent healthy tissue samples were collected. The concentrations of capecitabine and its metabolite 5-FU were determined by HPLC. The concentration-time profiles of capecitabine and 5-FU were fitted by pharmacokinetic model. The tissue distribution factors for capecitabine and 5-FU, and the AUC ratios of 5-FU to capecitabine in plasma, tumor or adjacent healthy tissue, were calculated with pharmacokinetic parameters, respectively. Results The Ka of capecitabine was 1.17 h^-1 in plasma, 0. 46 h^-1 in tumor tissue, and 0. 61 h^-1 in healthy tissue. The AUCs of capecitabine were 2. 557 1 μg·mL^-1 ·h, 1. 629 2 μg·g^-1·h and 2. 085 0 μg·g^-1· h, and T1/2 was 0. 782 3 h, 1. 528 1 h and 1. 289 6 h in plasma, tumor, and healthy tissue, respectively. The AUCs of 5-FU were 0.418 7 μg·mL^-1 h, 1.671 7 μg·g^-1·h and 1.020 8 μg·g^-1·h; the T1/2 was 0. 631 3 h ,1.204 1 h and 1.031 2 h in plasma, tumor, and healthy tissue, respectively. The tissue distribution factors of capecitabine were 0. 637 1 in tumor （AUCcap-Tumor/AUCcap-plasma） and 0. 851 4 in healthy tissue （AUCcap-HT/AUCcap-plasma . The tissue distribution factors of 5-FU were 3. 992 6 in tumor （AUC5-FU-Tumor/AUC5-FU-plasma） and 2. 438 0 in healthy tissue （AUC5-FU-HT/AUC5-FU-plasma）. The AUC ratios of 5-FU to capecitabine were 0. 1637, 1. 0261, and 0. 489 5 in plasma, tumor, and healthy tissue, respectively. Conclusion The simulation curves for the disposition of capecitabine and its metabolite 5-FU in plasma and tissue basically describe the activation process of capecitabine metabolizing to 5-FU and 5-FU elimination. There are similar distributions for capecitabine in plasma, tumor, and healthy tissue. The exposure of 5-FU in tumor was found to be 3. 992 6 times greater than that in plasma and 2. 438 0 times greater than that in healthy tissue. Capecitabine may metabolize preferentially to 5- FU in tumor tissue after oral administration.
基金Supported by Financial Project from Ministry of Agriculture(2014-2130135)Specia Fund for Basal Scientific Research of Central Public-interest Scientific Institutes,Beijing Institute of Animal Husbandry and Veterinary,Chinese Academy of Agricultura Sciences(2014ywf-yb-7)~~
文摘Myocyte enhancer factor 2B （MEF2B） gene belongs to myocyte enhancer factor 2 （MEF2） gene family. They are all widely expressed in muscle and nerve tissues of human and animals. MEF2B plays an important role in the growth of muscle, development and differentiation of nerve system and liver fibrosis. This re- view mainly focused on the structural characteristics, tissue distribution, biological functions and research progress of MEF2B gene in human and animals.
基金National Natural Sciences Foundation of China(Grant No.30371669)National High Technology Research and Development Program of China(863 Program,Grant No.2003AA2Z347B).
文摘The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.
文摘The author will propose that qualia--typically understood as the purely subjective and phenomenal elements of experience--are not specifically brain processes, but are instead best thought of as world processes that can be characterized as distributed self-organizing networks of Whiteheadian actual entities. If this is correct, then we need not wrestle with the materialist＇s ＂hard problem＂ of explaining how consciousness can arise from the purely objective particles and forces of fundamental ptiysics, but we will need to explain in what sense microparticles and other physical objects are experiential and objectively real without embracing panpsychism. Since Whiteheadian actual entities have intrinsic natures grounding the subjective and phenomenal aspects of experience, and extrinsic relations grounding objective physical properties, we find that qualia, understood in light of Whiteheadian actual entities, can provide the metaphysical foundations for both the subjective and objective aspects of the world.
基金Foundation for Distinguished Young Talents in Higher Education of Guangdong and Foundation for Young Scholars of Guangdong Medical College(Grant No XQ0802)
文摘An HPLC method for the determination of isovitexin in rat plasma and different tissues was developed.The separation was achieved on a C_（18）column with a mobile phase consisting of methanol-1% acetum（40：60,v/v）at a detection wavelength of 338 nm and a column temperature of 30℃.Rutin was chosen as the internal standard.The linear range of the standard curves was 0.20-128.75μg/mL in the plasma and 0.024-3.09μg/mL in the tissues.The LOQ was 0.19μg/mL in the plasma and 0.024μg/mL in the tissues.The relative recoveries of isovitexin ranged from 93% to 105% in the plasma and 87% to 112% in the tissues.The intra-and inter-day precisions were all below 8%.The pharmacokinetics and tissue distribution of isovitexin in rats were studied with the method.Blood samples were collected at fixed time intervals after the i.v.injection of isovitexin at a dosage of 18.75,3.75 and 0.75 mg/kg;the tissue samples（brain,liver,kidney,heart,lung,spleen and ovary）were obtained at 10,30,and 60 min after the i.v.injection of isovitexin at a dosage of 18.75 mg/kg.The pharmacokinetics of the isovitexin in three different dosages in the rats fit the two-compartment open model.The isovitexin displayed linear dynamics in the dosage range of 0.75-18.75 mg/kg.The mean value of t_（1/2α）was 1.54-1.84 min,and t_（1/2β）was 36.94-46.27 min at the three dosages.The tissue distribution study showed that the sequence of tissue drug concentration from high to low was kidneyliverlung≈ovaryheart≈spleenbrain.
文摘Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.
基金National Science and Technology Major Projects for"Major New Drugs Innovation and Development"(Grant No.2017ZX09301016)
文摘Brucine has anti-inflammatory and analgesic effects and is the main active compound of the seeds of Strychnos nux-vomica L. To study brucine niosomal gels, a reliable and rapid LC-MS/MS method was established to quantify brucine levels in rats. Tissue distribution and pharmacokinetics of brucine were investigated after topical and oral application of brucine niosomal gels to rats. The plasma concentration versus time profiles suggested that systemic exposure of brucine for oral administration of brucine niosomal gels was higher than that for topical administration, and topical administration showed a relatively sustained release. There was a considerable amount of brucine distributed in the knee joint. These results provided a strong basis for the follow-up study of this preparation.
基金The Scientific Research Fund Project of Heilongjiang University of Chinese Medicine(Grant No.201408)
文摘As an important bis-benzylisoquinoline alkaloid isolated from the bulbous root ofStephania tetrandra S. Moore, tetrandrine （Tet） is widely used for the treatment of malignant tumor due to its properties of reversing the multidrug resistance and apoptosis induction. In the present study, we aimed to evaluate the pharmacokinetics, tissue distribution and excretion of Tet in rats. Drug concentration in plasma and tissues was measured by high performance liquid chromatography （HPLC）, and the experimental data were analyzed using pharmacokinetic software DAS 2.0. The results showed that the plasma protein binding rate of Tet was 68.7%, indicating a higher protein binding drug. Tissue distribution was found in a descending order as follows： lung〉heart〉liver〉kidney〉spleen. Renal excretion was a major route of excretion, and the urine, bile and fecal excretion accounted for 25.73% of the administered dose. A UC0-∞ of Tet in the liver was 20 times greater than that in plasma, indicating that Tet had a higher affinity for the liver. Moreover, CL in the liver was the lowest among all tissues, indicating that Tet with slow elimination might result in the accumulation. Therefore, we need to adjust the dose for patients who have dysfunction in liver and kidney. In addition, therapeutic drug monitoring in long-term clinical treatment, if necessary, should be carried out.
