培哚普利叔丁胺中差向异构体分离测定方法研究

目的:建立一种快速液相色谱方法分离培哚普利叔丁胺及(±)-1”-差向-培哚普利叔丁胺(差向异构体),并对该差向异构体进行测定。方法:采用Agilent Poroshell CS-C₁₈(100 mm×3.0 mm, 2.7μm)色谱柱,以0.15%庚烷磺酸钠溶液(磷酸调节pH 2.0)-乙腈/戊醇(217∶3)(82∶18)为流动相,流速0.8 mL·min^-1,柱温50℃,进样量2μL,在215 nm波长处分离培哚普利及(±)-1”-差向-培哚普利。结果:培哚普利及(±)-1”-差向-培哚普利在25 min内依次出峰,峰谷比和分离度满足测定要求。培哚普利叔丁胺及其差向异构体均在2～2 000μg·mL^-1范围内线性关系良好(r>0.999),定量限(S/N约10)和检测限(S/N约3)均分别约为1.0μg·mL^-1和0.3μg·mL^-1。差向异构体低、中、高3个浓度的平均加样回收率为97.2%(RSD=1.8%,n=9)。10批样品中(±)-1”差向-培哚普利叔丁胺含量...     

旋光法测定培哚普利叔丁胺盐及培哚普利片含量

目的:建立培哚普利叔丁胺盐及培哚普利片含量测定方法。方法:以乙醇为溶剂,采用旋光法测定培哚普利叔丁胺盐及培哚普利片含量。结果:培哚普利叔丁胺盐在1.2~15 mg/ml范围内浓度与旋光度呈良好线性关系,回归方程C=0.005 4 1.468 8X,r=1.000 0,平均回收率99.6%,RSD为0.19%(n=9)。结论:本法简便易行,结果准确,可作为培哚普利叔丁胺盐及培哚普利片的质控方法。     

HPLC—MS／MS法测定人血浆中赖诺普利的浓度

目的:建立测定人血浆中赖诺普利浓度的 HPLC-MS/MS 法。方法:200μL待测血浆中定量加入内标后,直接加入蛋白沉淀剂三氟醋酸,涡旋离心后取上清液直接进样。采用 Zorbax Eclipse DB-C_8柱(5μm,150 mm×4.6 mm)分析柱;流动相为甲醇-12.5 mmol·L~(-1)醋酸铵缓冲液(60:40,pH=4.40),流速0.5 mL·min~(-1);进样量25μL。质谱检测采用 ESI 正离子模式,扫描方式为多反应监测方式,扫描离子对为 m/z406.3→84.0(赖诺普利)和 m/z 349.1→206.1(内标依那普利拉)。结果:本文所建立测定赖诺普利的线性范围为1.064～851.2 ng·mL~(-1),最低定量限可达1.064 ng·mL~(-1)。测定的方法回收率为97.52%～103.2%;日内 RSD<7%,日间 RSD<5%。结论:本文所建立的方法灵敏度良好、准确度高,可用于赖诺普利的药代动力学研究及临床药物浓度监测。     

培哚普利精氨酸盐与培哚普利叔丁胺盐治疗原发性轻中度高血压的疗效对比

目的:分析培哚普利精氨酸盐与培哚普利叔丁胺盐治疗原发性轻中度高血压的疗效.方法:选取2015年5月～2016年5月我院收治的108例原发性轻中度高血压患者为研究对象,随机给予54例5mg培哚普利精氨酸盐治疗,归为实验组,给予另54例5mg培哚普利叔丁胺盐治疗,归为对照组.采用双盲实验治疗,根据治疗八周后的血压情况调整用药量,给予舒张压高于90mmHg或收缩压高于140mmHg的患者增加5mg培哚普利精氨酸盐或5mg培哚普利叔丁胺盐,继续进行双盲实验治疗,四周后比较两组的疗效.结果:两组不良事件发生率均较低,且两组在治疗八周时和治疗十二周时的疗效及血压达标率相当.结论:培哚普利精氨酸盐与培哚普利叔丁胺盐治疗原发性轻中度高血压的疗效相当,且药物副作用少,安全有效,患者耐受性强.     

HPLC-MS/MS法同时测定人血浆中依那普利和依那普利拉的浓度

目的建立人血浆中依那普利和依那普利拉含量测定的高效液相色谱-串联质谱(HPLC-MS/M S)方法。方法血浆样品加入内标(贝那普利拉),以含0.1%甲酸的甲醇沉淀蛋白后,进行HPLC-M S/M S分析。色谱柱为Hedera ODS-2 C18(150 mm×2.1 mm,5μm),流动相为甲醇-0.5%甲酸水溶液梯度洗脱,流速为0.4 m L/min,柱温为30℃,采用多反应监测(M RM)方式进行定量分析,用于监测的离子质荷比分别为m/z377.2→m/z 234.3(依那普利)、m/z 349.3→m/z 206.2(依那普利拉)和m/z 397.4→m/z 351.4(内标,贝那普利拉)。结果人血浆中依那普利和依那普利拉的线性范围分别为0.2~200 ng/m L(r=0.999 9)、0.5~120 ng/m L(r=0.999 3);批内、批间精密度均<11.3%。结论该方法快速、灵敏、专属性强,可用于人血浆中依那普利和依那普利拉浓度的测定。     

培哚普利联合氨氯地平对老年高血压左室结构及功能的影响

目的:探索血管紧张素转换酶抑制剂培哚普利联用钙拮抗剂氨氯地平对逆转老年高血压病患者左室结构及功能影响。方法:老年高血压LVH患者46例,口服氨氯地平5m g/d、培哚普利4m g/d共6个月,观察血压、左室结构和功能改变。结果:培哚普利联合氨氯地平治疗后,收缩压(SBP)和舒张压(DBP)明显降低(P<0.01);二尖瓣E/A峰速度比值明显升高;舒张末期左室内径(LVD d)、室间隔厚度(IV ST)、左室心肌重量(LVM)、左室后壁厚度(LVPW T)、左室心肌重量指数(LVM I)均显著下降。结论:培哚普利联合氨氯地平能有效地效降压,并同时逆转左室肥厚,改善左室舒张功能。     

高血压患者内皮素水平变化及培哚普利对其影响

目的 :了解高血压 (EH)患者不同时期血浆内皮素 (ET)水平变化及培哚普利对其影响。方法 :选择HE组患者 6 3例与健康对照组 35组例 ,测定两组受试者血浆ET水平 ,同时给予EH组患者培哚普利 4mg ,口服 ,每日 1次 ,连服 8周 ,复查其血浆ET水平。结果 :EH组患者血浆ET水平较正常对照组明显增高 (P <0 0 5 ) ,且随分期逐级增高。培哚普利治疗 8周后 ,血浆ET水平显著下降 (P <0 0 5 )。结论 :EH的发生、发展与ET密切相关 ,培哚普利在有效降压的同时可显著降低血浆ET水平。     

高血压患者内皮素水平变化及培哚普利对其影响

目的：了解高血压（EH）患者不同时期血浆内皮素（ET）水平变化及培哚普利对其影响。方法：选择HE组患者63例与健康对照组35组例，测定两组受试者血浆ET水平，同时给予EH组患者培哚普利4mg，口服，每日1次，连服8周，复查其血浆ET水平。结果：EH组患者血浆ET水平较正常对照组明显增高（P＜0．05），且随分期逐级增高。培哚普利治疗8周后，血浆ET水平显著下降（P＜0.05）。结论：EH的发生、发展与ET密切相关，培哚普利在有效降压的同时可显著降低血浆ET水平。     

培哚普利治疗高血压病76例

目的 :通过与卡托普利对比 ,评价培哚普利治疗高血压的疗效 ,以及对血清总胆固醇 (TC)、三酰甘油 (TG)、血糖 (Glu)、肌酐 (Cr)等的影响。方法 :回顾性分析 12 6例 1～ 2级高血压病患者的临床资料 ,培哚普利组 76例 (培哚普利 2～ 4mg ,qd) ;卡托普利组 5 0例 (国产卡托普利 2 5～ 5 0mg ,tid)。疗程均为 4wk ,治疗前后有水银柱血压计的偶测BP和 2 4h动态BP记录 ,以及清晨空腹测量血清TC ,TG ,Glu ,Cr等指标。结果 :2组治疗后偶测BP ,2 4h平均BP和BP负荷均明显降低 ,培哚普利组的总有效率明显高于卡托普利组 (96 1%vs80 % ,P <0 0 5 ) ,峰谷比值培哚普利也明显优于卡托普利 (SBP :6 8 6mmHgvs 4 8 7mmHg ,DBP :70 2mmHgvs 5 1 4mmHg ,P <0 0 5 ) ,2组刺激性咳嗽的发生率类似 (15 8%vs 18% ,P >0 0 5 )。培哚普利组治疗后TG ,Glu比治疗前明显降低。结论 :培哚普利是一种安全有效的控制高血压的药物 ,疗效明显优于国产卡托普利 ;并能够改善高血压病患者的血糖和脂质代谢     

非巯基血管紧张素转换酶抑制剂培哚普利

血管紧张素转换酶 ( angiotensin converting en-zyme,ACE)抑制剂在治疗心力衰竭和高血压中具重要的作用。近来研究显示 ,它们在调节动脉粥样硬化和改善内皮细胞功能方面也可能有作用。培哚普利 ( perindopril)是一种非巯基 ACE抑制剂 ,作用强 ,持续时间久 ,临床上具一些潜在的优点[1,2 ] 。1　药物动力学培哚普利是一种前药 ,在体内迅速代谢为活性二酸培哚普利拉。口服给药 ,吸收迅速、完全 ,生物利用度高于 70 % ,且不受食物影响。活性代谢物在 3～4h内达峰值浓度 ,高峰药理活性 4～ 6h出现。前药和代谢物均为低分布容积 ,与蛋白仅有微…     

PERMEABILITY OF THE DEVELOPING AND MATURE BLOOD-BRAIN BARRIERS TO THEOPHYLLINE IN RATS

1. In the present study, the uptake of theophylline and L-glucose into the adult and neonatal rat brain has been investigated. Steady state cerebrospinal fluid (CSF) and brain concentrations of theophylline were reached within 1 h following a single intraperitoneal (i.p.) injection, whereas steady state CSF and brain concentrations of L-glucose were not approached until after 5 h. 2. Steady state brain:plasma and CSF:plasma concentration ratios for theophylline and L-glucose in neonatal rats were significantly higher than ratios in adult rats. Erythrocyte:plasma ratios for theophylline in neonatal rats were also significantly higher than ratios in adult rats. Steady state ratios for theophylline were significantly higher than those for L-glucose in both neonatal and adult rats. 3. Respiratory acidosis (pH 6.9–7.0) did not affect steady state CSF:plasma or brain.-plasma ratios for theophylline in neonatal or adult rats. In contrast, steady state CSF:plasma and brain:plasma ratios for L-glucose were increased by respiratory acidosis. 4. The lower steady state CSF:plasma, brain:plasma and erythrocyte:plasma ratios for theophylline in adult rats are likely to be due to a higher concentration of plasma proteins in adult blood compared with neonates, with a greater retention of protein-bound (non-exchangeable) theophylline in adult blood, and are unlikely to be due to p-glycoprotein-mediated efflux of theophylline at the adult blood-brain barrier.     

浅低温对大鼠血浆中精氨酸加压素、血管紧张素Ⅱ含量的影响

目的：探索不同低温条件下大鼠血浆AVP、AngⅡ含量的变化机制,为内分泌及低温领域提供一定的理论基础。方法：本实验采用低温模型,使用放射免疫法观察以下指标。结果：与对照组相比,实验各组AVP、Ang Ⅱ差异具有显著性（P＜0．01）,其中8℃-10℃组和－1℃--2℃组显著升高,2℃-4℃组显著下降,结论：浅低温可明显影响AVP、Ang Ⅱ含量的变化,AVP、AngⅡ参与体温调节。     

高效液相色谱法同时测定血浆中绿原酸和头孢唑啉

目的：建立同时测定绿原酸和头孢唑啉血浆浓度的高效液相色谱法。方法：色谱柱：Ｓｐｈｅｒｉｓｏｒｂ Ｃ１８;流动相：甲醇－０．１ｍｏｌ／Ｌ磷酸二氢钾（３０：７０,ｖ／ｖ）,磷酸调节 ｐＨ值至３;流速：１．２ｍｌ／ｍｉｎ;检测波长：２７５ｎｍ（绿原酸）和３２６ｎｍ头孢唑啉）。测定大鼠静脉给药的血浆浓度。结果：药物浓度与峰高线性关系良好（ｒ＝０．９９７和０．９９８）;绿原酸日内和日间ＲＳＩ）均小于４％,头孢唑啉日内和日间ＲＳＩ）均小于６％;两种药物高、中、低浓度平均加样回收率分别为９３．３０％、９３．３５％、９６．４０％和９３．４１％、９６．６０％、９２．３６％。与绿原酸合用降低体内头孢唑啉浓度。结论：该法适于绿原酸和头孢唑啉血浆浓度的同时监测。     

血浆内毒素定量测定及在感染性疾病中的应用

目的：初步建立血浆内毒素定量检测模式,提出健康人群血浆内毒素正常值及内毒素血症诊断参考值。方法：用稀释加热法排除血浆干扰,以弃G因子鲎试剂在BET－16细菌内毒素测定仪下检测被试者血浆内毒素水平,并将结果与临床病原微生物培养比较。结果：该法强化内毒素回收率50％－150％,符合FDA1987年版要求。在临床感染91例患者中,内毒素血症37例,全部分离出＞1株的G^-杆菌,其余54例血浆内毒素正常的患者中,只有5例分离出G^-杆菌。结论：该法快速,简便,可作为G^-杆菌感染及内毒素血症的诊断方法。     

蝙蝠葛苏林碱在兔血浆浓度监测及药代动力学蝙蝠葛苏林碱在兔血浆浓度监测及药代动力学

目的建立测定血浆中蝙蝠葛苏林碱浓度的方法,并研究蝙蝠葛苏林碱在家兔体内的药代动力学。方法 以蝙蝠葛碱作为内标。血浆样品经乙腈去蛋白,再用二氯甲烷两次萃取,采用RP-HPLC方法检测。结果血浆药物浓度在0.05～20.00 mg·L^-1线性关系良好(r=0.999 6),最低定量浓度为0.05 mg·L^-1,绝对回收率均大于80%,相对回收率为(101±5)%,精密度试验的日内及日间RSD%分别为1.9%～5.6%和3.5%～6.5%。药代动力学研究表明,家兔蝙蝠葛苏林碱单剂量iv后,其体内血药浓度时间数据符合二房室开放模型。结论本方法专属性强、灵敏度高、回收率高、重现性好,可用于蝙蝠葛苏林碱血药浓度测定及药代动力学研究。     

糖尿病患者合并高血压与胰岛素抵抗血浆肾上腺髓质素内皮素变化的关系

目的:探讨胰岛素抵抗、血浆肾上腺髓质素、内皮素与糖尿病合并高血压的关系.方法:测定36例血压正常及38例合并高血压糖尿病患者和对照组30例空腹血糖、空腹血浆胰岛素、肾上腺髓质素、内皮素水平.结果:合并高血压糖尿病患者存在胰岛素抵抗,血浆肾上腺髓质素、内皮素较血压正常者升高.结论:胰岛素抵抗、血浆内皮素升高是引起糖尿病患者血压升高的重要原因,血浆肾上腺髓质素升高是体内血压自身调节、防止血压进一步升高的一种代偿性保护机制.     

The distribution pattern of radioactivity across different tissues in quantitative whole-body autoradiography (QWBA) studies.

This study explored whether common rules exist for the distribution patterns across tissues in tissue distribution studies. To investigate this we tested whether tissue:plasma partition coefficients (PCs) of radioactivity are correlated with muscle:plasma PCs. The relationships between PCs of radioactivity in muscle and those in other tissues were investigated in 25 tissues for 20 structurally unrelated drug candidates. Tissue distribution data were obtained by quantitative whole-body autoradiography. Linear regression analysis was performed for each tissue. Radioactivity from basic and acidic/neutral compounds was analyzed separately. Results for acidic/neutral compounds: for the majority of the tissues investigated, the tissue:plasma PCs were well correlated with muscle:plasma PCs (R2 > 0.7). Correlations were worse (R2 < 0.7) in blood, white fat, excretory organs and tissues protected by a penetration barrier (e.g. brain). Slope factors for the regression ranged from 0.2 (blood) to 3.8 (Harderian gland) and were correlated with neutral lipid contents in tissues. Results for basic compounds: in most tissues, slope factors appeared to be higher than for acidic/neutral compounds. Correlations, however, were poorer than for acidic/neutral compounds. Overall, the present study demonstrates that muscle:plasma PCs are indicative of the overall tissue distribution of drug-related material, as they are well correlated with tissue:plasma PCs in most other tissues. Correlations for acidic/neutral compounds differ from those for basic compounds. The found PC relationships provide an explanation for the distribution pattern across tissues usually seen in tissue distribution studies.     

功能性消化不良患者胃肠激素水平的变化

目的：探讨胃肠激素水平的变化在功能性消化不良（FD）发病机制中的作用。方法：用放射免疫法（RIA）同批测定功能性消化不良患者（FD组）和健康志愿者（HC组）空腹血浆胃动素（MTL）及生长抑素（SS）的浓度。结果：FD组的MTL水平明显低于HC组，而FD组的SS水平明显高于HC组，具有统计学意义（P〈0．05）。结论：FD患者存在促胃肠运动和抑制胃肠运动激素的分泌失调，这些胃肠激素分泌失凋可能在FD的发病机制中起着一定的作用。     

长期服用氢氯噻嗪后RAAS活性变化与血糖变化关系

目的:探讨长期服用氢氯噻嗪(HCTZ)后肾素-血管紧张素-醛固酮系统(RAAS)活性变化与血糖(GLU)变化之间的关系。方法:选择119例高血压患者,测定基线RAAS活性和GLU水平等指标后,给予HCTZ12.5mg,qd,1年后测定RAAS活性和GLU水平,分析服用HCTZ1年后RAAS活性变化与GLU水平之间的关系。结果:服用HCTZ1年后,血清肾素活性(PRA)水平升高组与不升高组患者GLU水平下降幅度分别是(-0.26±0.26)mmol·L-1、(-1.36±0.23)mmol·L-1,差异有统计学意义(P<0.05);血清血管紧张素Ⅱ(AngⅡ)水平升高组与不升高组患者GLU水平下降幅度分别是(-0.17±0.18)mmol·L-1、(-1.07±0.21)mmol·L-1,差异有统计学意义(P<0.05)。服药后AngⅡ水平升高的患者中,GLU水平同时也升高的人数比例(40.5%)明显高于AngⅡ水平不升高患者中的相应患者比例(16.9%),差异有统计学意义(P<0.05)。校正年龄、性别、基线GLU水平等其他因素影响后,服用HCTZ1年后的血清AngⅡ水平变化与GLU水平变化独立相关。结论:服用HCTZ1年后的RAAS活性变化与GLU变化之间存在相关关系。     

Simulation of the onset of neuromuscular block based on the early oscillations in the arterial plasma concentrations

Objective: The aim of the study was to describe by simulation the true plasma concentrations of nondepolarizing muscle relaxants (NDMRs) as a continuous function of time. In contrast to standard pharmacokinetic analysis of the time course of action via extrapolated plasma concentrations, the derived curve was to reflect zero plasma concentration initially and one or more cycles of peaks and troughs subsequently. We desired to study the influence of the initial delay and the early oscillations in the plasma concentrations on the time to onset of peak but submaximal neuromuscular block (NMB). Hypothetical NDMRs were postulated to display in humans a pattern of early arterial plasma concentrations similar to the reported pattern of indocyanine green plasma concentrations in dogs (an initial delay period and subsequent peaks and troughs). Methods: Two hypothetical NDMRs with either a very rapid or a slow decay in plasma concentrations were used for the simulations. A delay and oscillations were imposed on a multiexponential function for the plasma concentrations of the NDMRs by an additional, biexponentially dampened sinusoid function. The time between intravenous bolus administration of the NDMRs and the first rise in plasma concentrations was fixed at 0.2 min. As experimentally observed with indocyanine green in dogs, the oscillations were limited to the first minute after injection. The NDMRs were simulated to diffuse from plasma into and out of the interstitial space of muscles according to a rate constant and the concentration gradient. The NDMRs were postulated to have free access from the interstitial space to the receptors, and the neuromuscular block was calculated using the Hill equation. Results: The delay and the peak and trough plasma concentrations during the first minute after bolus injection of the NDMRs were simulated well by the postulated dampened sinusoidal function. The times to peak submaximal NMB and the equieffective doses were similar whether calculated on the basis of oscillatory or extrapolated multiexponential functions. Both simulations demonstrated that a rapid initial decay of the plasma concentrations is associated with a slightly faster onset of peak NMB and a slightly higher equieffective dose. Conclusion: Consideration of early oscillations in the plasma concentrations of a NDMR barely alters the simulated time course of action from that simulated by an extrapolated multiexponential function. Received: 1 July 1996 / Accepted: 12 November 1996