冬凌草甲素在不同种属血浆中蛋白结合率的HPLC法测定

目的:建立冬凌草甲素在大鼠血浆、人血浆和牛血清白蛋白中蛋白结合率的测定方法,并计算不同种属血浆蛋白的相关参数。方法:采用HPLC法测定血浆中药物总浓度及游离药物浓度,应用平衡透析法测定蛋白结合率。结果:大鼠血浆中冬凌草甲素高、中、低3个浓度的血浆蛋白结合率分别为(69.66±12.8)%,(59.62±12.6)%,(57.94±4.1)%;人血浆中冬凌草甲素高、中、低3个浓度的血浆蛋白结合率分别为(78.15±3.6)%,(77.92±8.8)%,(76.72±7.3)%;牛血清白蛋白中冬凌草甲素高、中、低3个浓度的血浆蛋白结合率分别为(35.58±7.2)%,(34.59±10.8)%,(32.03±6.0)%。结论:在体外冬凌草甲素与大鼠血浆、人血浆和牛血清白蛋白属中等结合型药物,且蛋白结合率随着药物血浆浓度的增加无明显的浓度依赖性。     

药物与血浆蛋白结合的竞争对用药有何影响?

<正> 多数药物经吸收,进入血液后能不同程度地与血浆蛋白进行可逆性结合,其中结合型药物失去活性,只有游离型药物才呈现药理活性。同时服用两种或两种以上的药物,如果它们都可与血浆蛋白的同一部位结合,则发生竞争现象,结合率高的药物可把结合率低的药物从血浆蛋白结合部位置换出来。这时,被置换出来的药物活性增强或引起中毒反应。一般来说,这一相互作用限于血浆蛋白结合率高、分布容积小及消除慢的药物。临床上,以下药物合用时应提高警     

中空纤维液相微萃取结合高效液相色谱法测定比索洛尔血浆蛋白结合率

目的将中空纤维液相微萃取技术与高效液相色谱法结合,建立测定比索洛尔血浆蛋白结合率的新方法。方法优化比索洛尔血浆样本的液相微萃取条件;利用高效液相色谱法测定比索洛尔在接受相中的浓度,色谱条件为水-甲醇-乙腈-0.1%磷酸(50∶34∶6∶10),检测波长Ex:232 nm,Em:300 nm,分别代入当日标准曲线计算出比索洛尔血浆游离药物浓度及总药物浓度,进而计算比索洛尔血浆蛋白结合率。结果在低、中、高3种浓度下测得比索洛尔的血浆蛋白结合率分别为31.2%,32.0%,31.8%。结论所建立的方法简便快速,重复性好,适用于药物游离浓度及血浆蛋白结合率的测定。比索洛尔与人血浆蛋白有中等程度结合,且不存在浓度依赖性。     

平衡透析法测定人体外血浆中原花青素B2、表儿茶素蛋白结合率

目的 建立检测原花青素B2、表儿茶素在血浆中药物浓度的方法,并测定其体外血浆蛋白结合率.方法 采用平衡透析法测定血浆蛋白结合率,建立HPLC法测定各成分的血药浓度及游离药物浓度,生物样本用乙酸乙酯溶液提取的方法.结果 在低、中、高3种浓度下,原花青素B2和表儿茶素在人体外血浆中的蛋白结合率分别为(44.21±2.80)%,(52.60±1.92)%,(48.11±3.09)%和(47.12±2.85)%,(55.03±2.47)%,(43.69±1.53)%.结论 采用HPLC法对原花青素B2、表儿茶素进行分离,方法简便、可靠、稳定.体外实验中原花青素B2和表儿茶素与人血浆属中等结合型药物,且蛋白结合率随着药物浓度的增加无明显的浓度依赖性.     

中药有效成分血浆蛋白结合率的研究进展与相关规律探讨

目的系统了解中药有效成分血浆蛋白结合率国内外研究进展,并探讨相关规律,为相关研究提供借鉴和参考,并为预测中药与其他药物联用时,是否会发生血浆蛋白结合介导的药物相互作用提供依据。方法通过文献检索,对中药有效成分血浆蛋白结合率的相关报道进行分析和总结。结果中药有效成分血浆蛋白结合率的研究国内外已有较多报道,显示不同结构的成分血浆蛋白结合率有较大差异,与结构类别、官能团位置、官能团数量等因素有关,且呈现一定的规律性。结论很多中药成分具有较高的血浆蛋白结合率,这些中药及其制剂与高血浆蛋白结合率的药物联用时,应关注可能会因为竞争血浆蛋白结合而产生药物相互作用,以保障患者用药安全。     

平衡透析法测定具栖冬青苷和毛冬青酸的大鼠血浆蛋白结合率

目的建立测定具栖冬青苷、毛冬青酸血药质量浓度的方法,并测定其大鼠体外血浆蛋白结合率。方法采用高效液相色谱法和平衡透析法测定具栖冬青苷、毛冬青酸在大鼠体外血浆中的血浆蛋白结合率。结果低、中、高3种质量浓度,具栖冬青苷在大鼠体外血浆中的蛋白结合率分别为39.72%±2.68%,52.05%±3.35%和52.32%±0.76%;毛冬青酸在大鼠体外血浆中的蛋白结合率分别为55.18%±3.66%,60.79%±2.20%和47.00%±1.59%。结论建立HPLC法对具栖冬青苷和毛冬青酸进行分离,方法简便。体外实验,具栖冬青苷和毛冬青酸与大鼠血浆属中等结合型药物,且蛋白结合率与药物质量浓度无关。     

阿托伐他汀在非酒精性脂肪肝治疗中的应用价值及不良反应分析

目的:分析非酒精性脂肪肝患者采用阿托伐他汀治疗的应用价值及对不良反应的影响.方法:选择非酒精性脂肪肝患者92例随机分成两组,对照组采用药物甘草酸二铵肠溶胶囊治疗,观察组在此基础上结合药物阿托伐他汀,对比两组患者的临床相关症状改善效果、不良反应发生率、肝脏弹性检测结果.结果:观察组的临床相关症状改善效果远优于对照组,该组的不良反应率(8.70％)远低于对照组(26.09％),其肝脏弹性检测的硬度数值也明显比对照组低,效果明显(P<0.05).结论:阿托伐他汀和甘草酸二铵肠溶胶囊两种药物结合治疗非酒精性脂肪肝的应用价值和降低不良反应效果显著.     

阿比朵尔人血浆蛋白结合率的测定

目的:建立测定阿比朵尔血浆药物浓度的高效液相色谱法(HPLC),并考察阿比朵尔的人血浆蛋白结合率。方法:采用平衡透析法结合HPLC,对阿比朵尔的人血浆蛋白结合率进行测定。结果:低、中、高3种浓度下,阿比朵尔的血浆蛋白结合率分别为90．1％,91．1％和89．8％。结论:本方法灵敏度高,重现性好,操作简单,能满足药品分析要求。阿比朵尔与血浆蛋白具有较强的结合。     

第三章 体内药学特性评价指南

1药代动力学 资料来源：药品说明书、注册资料、企业申报材料、FDA／SFDA等政府网站等。 1．1关注药物蛋白结合率与分布特性。对蛋白结合率90％以上的药物，注意其蛋白结合与置换、导致游离药物浓度升高的相互作用。     

美沙拉嗪PEG化前药在不同种属血浆中蛋白结合率的测定

目的:测定美沙拉嗪PEG化前药在不同种属血浆中的蛋白结合率,考察PEG化对药物蛋白结合率的影响。方法:采用血浆平衡透析法,以紫外分光光度法对透析内液与外液中的药物含量进行测定,计算药物与小鼠血浆、犬血浆、兔血浆及牛血浆的蛋白结合率。结果:美沙拉嗪PEG化物的低、中、高(1.08,1.35,1.62 mg·mL^-1)3种质量浓度的小鼠血浆蛋白结合率分别为(22.31±5.28)%,(17.15±3.21)%,(16.11±4.55)%;犬血浆为(25.16±5.87)%,(22.47±4.14)%,(23.14±3.46)%;兔血浆为(17.13±8.26)%,(13.87±6.32)%,(15.93±2.31)%;牛血浆为(14.41±6.21)%,(18.84±7.80)%,(14.18±5.23)%。结论:美沙拉嗪PEG化物血浆蛋白结合程度较低,种属间存在一定差异。与原型药物相比,药物经PEG化后,血浆蛋白结合呈下降趋势。     

基于多元线性回归的癫痫患儿丙戊酸血药浓度影响因素分析

目的：探讨影响癫痫患儿丙戊酸（VPA）的血药浓度的因素。方法：回顾性分析我院218例VPA血药浓度监测报告,包括患儿性别、年龄、丙戊酸钠日总剂量、联合用药情况、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血浆白蛋白、血肌酐和稳态血药浓度。利用多元线性回归分析影响VPA血药浓度变化的因素。结果：多元线性回归分析显示,日总剂量与血药浓度呈正相关（P<0.05）,白蛋白含量与血药浓度呈负相关（P<0.05）,不同剂型对血药浓度有影响,丙戊酸钠缓释片与糖浆的血药浓度比较差异有统计学意义（P<0.05）。结论：丙戊酸钠的不同剂型、给药剂量和白蛋白含量会影响VPA血药浓度,患儿性别、年龄、是否联用左乙拉西坦或拉莫三嗪、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血肌酐与血药浓度无相关性     

87例肾脏疾病患者血清Cystatin C与肌酐测定评价分析

目的：评价血清半胱氨酸蛋白酶抑制剂-C（Cystatin C）对肾脏损害患者肾小球滤过功能的临床应用价值。方法：采用胶乳增强免疫透射比浊法分别测定49例正常人和87例肾病患者血清Cystatin C浓度，同时测定血清肌酐（Scr）及内生肌酐清除率（Ccr），将血清Cystatin C与Scr和Ccr相比较。结果：Cystatin C水平随内生肌酐清除率下降逐渐升高。在不同肾病组Cystatin C的阳性检出率与Scr和Ccr的阳性检出率相比差异有显著性（P〈0．01）。Ccr〉80ml／min肾病患者有55％显示Cystatin C异常。结论：Cystatin C比Scr更能够反应肾脏滤过功能的损害。可替代内生肌酐清除率作为判断肾小球滤过功能的指标。     

Differentiated effects of liver cirrhosis on the albumin binding sites for diazepam,salicylic acid and warfarin

The protein binding of diazepam, salicylic acid and warfarin in serum of patients with liver cirrhosis has been studied by equilibrium dialysis and circular dichroism measurements and compared with that in normal serum. Diazepam and warfarin are mainly bound to two separate sites on the serum albumin molecule and salicylic acid to both sites. The binding of diazepam and salicylic acid was impaired in serum from the patients when compared with the binding in serum from healthy individuals, while the binding of warfarin was unchanged. The results were the same when the binding was studied with albumin isolated from patient serum and normal serum. After treatment of the albumin with charcoal at pH 3, however, the binding was improved.The apparent binding constants of the drugs in serum both from patients with liver cirrhosis and from healthy persons were increased by dilution of the sera in buffer. This effect is due to the presence of competitive inhibitors in the sera. The decreased binding of diazepam and salicylic acid in the serum from the patients with liver cirrhosis can in addition be related to the presence of allosteric inhibitors specifically affecting the diazepam binding site on albumin, while the warfarin site apparently is unaffected.     

抗精神病药物对女性精神病患者血清催乳素的影响研究

目的分析几种抗精神病药物对女性精神病患者血清催乳素的影响。方法将164例女性精神分裂症患者随机分成4组,每组各41例。分别进行阿立哌唑、利培酮、奥氮平以及舒必利治疗,均治疗9周,并将所有患者治疗后的血清催乳素水平与治疗前相比较。结果患者经过四种药物治疗后精神状况均明显好转,但作为女性患者来讲,有些药物对于患者的催乳素水平有一定的影响。相比之下,用阿立哌唑治疗的患者不良反应较轻,催乳素前后变化最小。结论利培酮、阿立哌唑、奥氮平、舒必利对女性精神病的治疗,均有很好的效果。但相比之下,用阿立哌唑治疗的患者的催乳素水平变化不明显。阿立哌唑对于女性精神病患者的催乳素影响较轻,建议将其广泛应用于医学领域。     

A comparative study of saliva and serum paracetamol levels using a simple spectrophotometric method.

The relationship between saliva and serum paracetamol levels was investigated in ten healthy male volunteers. The salivary and serum paracetamol levels showed significant correlation with each other. The salivary and serum paracetamol concentration ratio was highly dependent on sampling time. The salivary and serum paracetamol half-lives showed significant correlation with each other while the area under curve of paracetamol concentration in saliva and serum failed to show significant correlation.     

急性脑梗死患者血清胱抑素C和C反应蛋白水平变化的研究

目的：探讨急性脑梗死患者血清胱抑素C（cystatin C,Cys-C）和C反应蛋白（CRP）水平对病情变化及预后判断的意义。方法选择颈动脉系统进展性脑梗死70例为进展组,非进展性脑梗死168例为非进展组,分别于入院次日（第1天）、第3、7和14天检测血清Cys-C和CRP浓度,行颈部血管超声和经颅多普勒超声（ transcranial Doppler sonography ,TCD）检查,以及卒中量表（ National Institutes of Health Stroke Scale ,NIHSS）和Barthel 指数（ Barthel index ,BI）评分。结果进展组患者入院时颅／颈动脉狭窄率高于非进展组（44．3％ vs 29．8％,P＜0．05）,非进展组患者血清Cys-C浓度在第7、14天下降,血清CRP浓度在第3、7、14天下降,进展组患者Cys-C和CRP浓度在第3天明显增加,Cys-C浓度在第14天下降,CRP浓度在第7、14天下降,明显高于非进展组（P＜0．01）。进展组NIHSS和BI评分在入院后进行性增高,非进展组NIHSS和BI评分呈下降趋势（ P＜0．01）。结论观察血清Cys-C及CRP浓度的变化有助于早期发现和及时处理进展性脑梗死。     

Cigarette smoke and N-acetylcysteine: interference with the bactericidal properties of serum

The bactericidal properties of normal serum are an important feature in host defence; it has been suggested that they are depressed by cigarette smoke. The aim of the present study was to investigate the in vitro depressant effect of cigarette smoke on antibacterial activity of rabbit serum and its interaction with the well-known antioxidant agent, N-acetylcysteine. Escherichia coli was used to study the bactericidal activity of the complement-dependent system and Staphylococcus aureus was used to study the thermostable bactericidal system. It was found that exposure of serum and bacteria to cigarette smoke significantly decreased the bactericidal powder of serum; when N-acetylcysteine was added to the incubation mixture, however, a marked inhibitory effect on the toxic action of smoke on rabbit serum was observed.     

Hyponatraemia in very old nonhospitalised people: association with drug use

OBJECTIVE: Hyponatraemia is one of the major problems in geriatric inpatients. However, in nonhospitalised elderly, the preponderance of hyponatraemia and the importance of the effect of drug intake on serum sodium concentrations are little known. This study investigated the prevalence of hyponatraemia in very old nonhospitalised people, controlling for factors that may induce hyponatraemia (especially drug use). METHODS: Data on serum sodium concentration, health and drug use were retrieved for 185 persons aged 92 to 93 years (the 1905 cohort) and 147 persons aged 100 years (the centenarian cohort) participating in two major population-based studies of elderly people in Denmark. Data were analysed by comparing median serum sodium concentrations between users and nonusers of various drugs after controlling for the influence of age, sex, cancer, heart failure, hypothyroidism, renal failure and smoking. Furthermore, the preponderance of drug use in the patients with clinically relevant hyponatraemia was compared with that in persons with normal serum sodium concentrations. RESULTS: Median serum sodium concentration was 140 mmol/L for the centenarians and 141 mmol/L for the 1905 cohort. In total, 19 persons had hyponatraemia (serum sodium concentration < or =134 mmol/L). There was no association between median serum sodium concentration and any of the above-mentioned diseases, or sex or smoking. Of the drugs generally known to cause hyponatraemia, only omeprazole and oral antidiabetic agents were associated with significantly lower median serum sodium concentrations (difference 3 mmol/L). Use of thiazide diuretics was significantly more common than expected in persons with hyponatraemia compared with persons with a normal serum sodium concentration (7 of 19 vs 46 of 270 individuals). Furthermore, the results suggested that digoxin and lactulose might be associated with a lowered median serum sodium concentration. CONCLUSION: This study demonstrates that severe hyponatraemia was rarely seen in a population-based sample of very old persons and that drugs have only a limited influence on serum sodium concentration. The only drug class associated with clinically relevant hyponatraemia was thiazide diuretics, which were used by significantly more persons with hyponatraemia. Furthermore, this study suggests that digoxin and lactulose use is associated with lower serum sodium concentrations in the elderly.     

Co-assessment of cell cycle and micronucleus frequencies demonstrates the influence of serum on the in vitro genotoxic response to amorphous monodisperse silica nanoparticles of varying sizes

Serum proteins have been shown to modulate the cytotoxic and genotoxic responses to nanomaterials. The aim was to investigate the influence of serum on the induction of micronuclei (MN) by nanoparticles (NPs) of different sizes. Therefore, A549 human lung carcinoma cells and amorphous monodisperse silica nanoparticles (SNPs) were used as models. Assessment of the cell viability, cell cycle changes and induction of MN by SNPs ranging from 12 to 174 nm was performed in presence or absence of serum, applying the in vitro flow cytometry-based MN assay. Here, it has been demonstrated that serum has an influence on these end points, with a lower cell viability in absence of serum compared with the presence of serum. Further, cell cycle changes, specifically, G₁ and S-phase arrest, were observed in absence of serum for four out of six SNPs tested. A size-dependent MN induction was observed: larger SNPs being more active in absence of serum. In addition, the serum influence was characterised by a size-dependency for cytotoxic and genotoxic effects, with a higher influence of serum for smaller particles. The data indicate that the in vitro micronucleus assay in presence and absence of serum could be advised for hazard assessment because it demonstrates a higher sensitivity in serum-free conditions than in conditions with serum. However, this recommendation applies only if the cell line used is able to proliferate under serum-free conditions because cell division is a prerequisite for MN expression.     

胱抑素C对3～6个月龄孕妇妊高征的预测价值分析

目的探讨胱抑素C对(3～6)个月孕龄孕妇妊高征的预测价值。方法选取孕龄(3～6)个月的妊高征孕妇485例,以及同期同孕龄健康孕妇515例。收集其血清,测定血清胱抑素C、血尿素、血肌酐、尿酸以及肌酐清除率进行测定。结果观察组孕妇孕(3～6)个月时血清胱抑素C含量为(1.51±0.20)mg/L,明显高于对照组(0.81±0.12)mg/L的血清含量;晚期诊断为轻、中、重度妊高征孕妇在(3～6)个月孕龄时所查血清胱抑素C含量均高于正常妊娠组,且随着程度加重,含量明显升高。上述比较差异均具有显著性(P值均<0.05)。结论胱抑素C对妊娠高血压综合征的诊断和严重程度有着预测作用,其敏感性明显高于血清肌酐等内源性指标,应用中应结合临床进行综合评估,提高母婴生活质量。