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31.
J. R. Bernstein B. M. Manzione R. C. Pohland R. B. Franklin 《Biopharmaceutics & drug disposition》1994,15(2):137-150
Tissue distribution studies, utilizing whole-body autoradiography and organ dissection techniques, were conducted in male Fischer 344 rats following the oral administration of 14C-dapoxetine HCl, a potent serotonin reuptake inhibitor. The preliminary study using whole-body autoradiography proved invaluable in locating radioactivity in an organ not usually harvested in a tissue distribution study, namely the preputial gland. Selected organs, based on whole-body autoradiography findings, were dissected from rats and analyzed for radiocarbon content by liquid scintillation counting and for parent drug and N-dealkylated metabolites by extraction and HPLC analysis. Highest concentrations of radiocarbon were observed in the organs of absorption and elimination (ileum, cecum, stomach, duodenum, liver, colon, and kidney) but notable quantities were observed in the lung and preputial and Harderian glands. Most tissues had returned to background radioactive levels 72 h after dosing but persistent concentrations of radiocarbon were present in the preputial gland and liver one week after the single dose of 14C-dapoxetine. Analysis by HPLC demonstrated the presence of parent drug and N-desmethyl metabolite (nor-dapoxetine) in those organs examined; however, the majority of the radioactivity remained unidentified. 相似文献
32.
Haiyung Cheng Jules I. Schwartz Charles Lin Raju D. Amin James R. Seibold Kenneth C. Lasseter David L. Ebel Dominick J. Tocco J. Douglas Rogers 《Biopharmaceutics & drug disposition》1994,15(5):409-418
MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD4-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg 14C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative. 相似文献
33.
Fast and slow twitch muscle fibers have distinct contractile properties. Here we determined that membrane excitability also varies with fiber type. Na+ currents (INA) were studied with the loose-patch voltage clamp technique on 29 histochemically classified human intercostal skeletal muscle fibers at the endplate border and <200 μm from the endplate (extrajunctional). Fast and slow twitch fibers showed slow inactivation of endplate border and extrajunctional INA and had increased INA at the endplate border compared to extrajunctional membrane. The voltage dependencies of INA were similar on the endplate border and extrajunctional membrane, which suggests thatboth regions have physiclogically similar channels. Fast twitch fibers had larger INA on the endplate border and extrajunctional membrane and manifest fast and slow inactivation of INA at more negative potentials than slow twitch fibers. For normal muscle, the differences between INA on fast and slow twitch fibers might: (1) enable fast twitch fibers to operate at high firing frequencies for brief periods; and (2) enable slow twitch fibers to operate at low firing frequencies for prolonged times. Disorders of skeletal membrane excitability, such as the periodic paralyses and myotonias, may impact fast and slow twitch fibers differently due to the distinctive Na+ channel properties of each fiber type. © 1993 John Wiley & Sons, Inc. 相似文献
34.
目的 研究12 5I标记的整合素αVβ3 拮抗多肽 (12 5I RGD 4CY)在小鼠体内的生物学分布及药物代谢动力学。方法 应用Iodogen法行12 5I标记RGD 4CY多肽 ,经小鼠尾静脉注射给药 ,分别在10、30、6 0、12 0和 2 4 0min不同时相点测量血液及各主要组织器官的放射性浓度 ,计算获得其体内生物学分布与药物代谢动力学数据。结果 RGD 4CY能够被12 5I有效标记 ;给药后在血液、肾脏、肝脏有较高的放射性分布 ,小肠、肺脏、肌肉呈低水平放射性分布 ;其分布相半衰期为 9.17min ,消除相半衰期为831min。结论 静脉注射12 5I RGD 4CY后 ,组织本底能够在较短的时间内达到低水平 ,血药浓度一时间曲线符合二房室模型特征 ,在体内的分布与消除为一级线性动力学过程。 相似文献
35.
Glycine is unique among the amino acids in view of its symmetric nature. While the overall distribution of glycyl residues in the (φ, ø) plane is near-symmetric, there can be certain preferences for the individual conformations. An analysis of the observed glycyl conformations in 70 proteins has been carried out to find the influence of residues adjoining the glycyl residues. For this purpose, the (φ, ø) plane has been divided into two regions: (a) the region in which φ is negative and (b) the region in which φ is positive. The analysis is done in terms of the number of conformations occurring in these regions. It has been found that while the overall percentage distribution of glycyl residues between the positive and the negative φ regions is 54:46, the distribution shows asymmetry when the examples are sorted out in terms of X-Gly and Gly-Y doublets. The asymmetry becomes more prominent when the data are sorted out into triplets X-Gly-Y. Using the available information, it has been possible to designate 25 triplets as P-predominant and 19 as N-predominant. An examination of P-predominant triplets for possible occurrence in β-bends having one of the conformations in the positive φ region shows that only 25% are of this nature. Thus, the P-preference of P-predominant triplets is not an outcome of the bend formation alone and must be an inherent property of these triplets. 相似文献
36.
基底动脉缝隙连接蛋白的分布 总被引:3,自引:0,他引:3
目的:探讨正常脑血管缝隙连接蛋白的分布。方法:采用RT—PCR、免疫组化方法测定多种缝隙连接蛋白在大白兔基底动脉的表达。结果:(1)RT—PCR发现大白兔基底动脉血管组织中至少存在Xx45、Cx43、Cx40和Cx37四种缝隙连接蛋白mRNA表达;(2)免疫组化证实Cx45和Cx43主要分布于血管内皮,平滑肌细胞间末见Cx45和Cx43的染色。结论:大白兔基底动脉血管组织存在丰富的缝隙连接蛋白的表达,与体内其它弹力血管相比,缝隙连接蛋白的分布模式有其特殊性。 相似文献
37.
In this paper, a vertical distribution of 137Cs in undisturbed soil was investigated experimentally and theoretically. Soil samples were taken from the surroundings of the city of Kragujevac in central Serbia during spring-summer of 2001. The sampling locations were chosen in such a way that the influence of soil characteristics on depth distribution of 137Cs in soil could be investigated. Activity of 137Cs in soil samples was measured using a HpGe detector and multi-channel analyzer. Based on vertical distribution of 137Cs in soil which was measured for each of 10 locations, the diffusion coefficient of 137Cs in soil was determined. In the next half-century, 137Cs will remain as the source of the exposure. Fifteen years after the Chernobyl accident, and more than 30 years after nuclear probes, the largest activity of 137Cs is still within 10 cm of the upper layer of the soil. This result confirms that the penetration of 137Cs in soil is a very slow process. Experimental results were compared with two different Green functions and no major differences were found between them. While both functions fit experimental data well in the upper layer of soil, the fitting is not so good in deeper layers. Although the curves obtained by these two functions are very close to each other, there are some differences in the values of parameters acquired by them. 相似文献
38.
6186例脑卒中患者发病时间的季节性分析 总被引:3,自引:0,他引:3
目的探讨青岛市区脑出血(CH)、脑梗死(CI)、蛛网膜下腔出血(SAH)发病时间的季节规律。方法收集青岛市1998年~2002年脑卒中患者6186例,其中CH1179人,CI4821人,SAH186人。圆分布分析探讨脑卒中患者发病时间的季节规律。结果CH冬季高发,平均角在1月份(P<0.05),男性患者的平均角在2月份(P<0.05),女性患者的平均角在1月份(P<0.05);CI秋季高发,男、女间无差别,平均角在10月份(P<0.05);SAH秋季高发,平均角在10月份(P<0.05),男性患者的平均角在9月份(P<0.05),女性患者的平均角在10月份(P<0.05)。结论青岛市的脑卒中发病具有季节性,在脑卒中预防工作中要充分考虑其发病的季节特点,并采取相应的措施。 相似文献
39.
S.L. CHARLES NGU PETER DUVAL CATHRYN COLLINS 《Journal of Medical Imaging and Radiation Oncology》1992,36(4):321-322
Management of breast cancer during pregnancy is complicated by the high risks of abortion and foetal malformation from the use of radio therapy and chemotherapy. A case of breast cancer during pregnancy, treated with radiotherapy, and the estimated foetal dose is reported. 相似文献
40.