伊贝沙坦与雷米普利对充血性心力衰竭疗效比较

目的比较伊贝沙坦与雷米普利对充血性心力衰竭(CHF)的临床疗效及安全性。方法72例CHF患者在常规治疗基础上随机分为2组。伊贝沙坦组(36例)口服伊贝沙坦150 mg.d-1;雷米普利组(36例)口服雷米普利2.5 mg.d-1。治疗前与治疗6 mo后分别用超声心动图测量左室射血分数(LVEF)、左室短轴缩短分数(LVFS)、每搏输出量(SV)、心排量(CO)、心脏指数(CI)评估心功能。结果治疗6 mo后,2组心功能较治疗前非常明显改善(P<0.01),2组之间比较差异无统计学意义(P>0.05)。结论伊贝沙坦与雷米普利治疗CHF均有效,且疗效相当。     

复方厄贝沙坦片中厄贝沙坦和氢氯噻嗪的HPLC测定

建立同时测定复方厄贝沙坦片中厄贝沙坦和氢氯噻嗪含量的HPLC方法。用Inertsil ODS-3色谱柱，流动相为乙腈-0．08mol／L磷酸溶液(用三乙胺调至pH5．0)(40：60)，检测波长225nm。厄贝沙坦和氢氯噻嗪分别在15～135μg／ml(r=0．9999)和1．2～10．8μg／ml(r=0．9999)浓度范围内线性关系良好，方法平均回收率分别为100．0％(RSD=0．46％)和100．5％(RSD=0．49％)。     

厄贝沙坦在健康志愿者体内的药代动力学-药效学结合模型

目的研究厄贝沙坦在健康志愿者体内的药代动力学-药效学结合模型,探讨其临床药效学特征。方法18例健康志愿者厄贝沙坦片口服给药,测定血药浓度,同时测量收缩压(SBP)、舒张压(DBP)及心率(HR)等药效指标。计算厄贝沙坦的药动学参数,并根据sheiner效应室模型理论,计算药效学参数。结果厄贝沙坦的血药浓度时间曲线呈二室模型;厄贝沙坦抑制SBP和DBP的效应滞后于血药浓度,药效与血药浓度之间存在逆时针滞后环,药效和效应室浓度的关系符合SigmoidEmax模型。厄贝沙坦抑制SBP和DBP的药效学参数Emax分别为(14.8±1.5)和(9.8±2.1)mmHg,EC50分别为(0.29±0.11)和(0.18±0.07)mg·L-1,Keo分别为(0.62±0.09)和(0.68±0.07)h-1。结论建立了厄贝沙坦在健康者体内的药代动力学-药效学结合模型,有利于临床合理用药。     

血管紧张肽Ⅱ受体拮抗剂的药动学与临床用药

血管紧张肽Ⅱ受体拮抗剂 (ARB)是一类在血管紧张肽Ⅱ 1型受体 (AT1受体 )水平拮抗血管紧张肽Ⅱ (ATⅡ )的降压药物。它们的药动学各具特色 ,因而具有不同的临床用药特点。氯沙坦 (losar tan)经细胞色素P 450 (CYP) 3A4及 2C9介导转化成其活性代谢物EXP31 74,故在肝功能不全时应减半量使用。替米沙坦 (telmisartan)的T1 / 2 最长 ,谷 /峰比最大 ,与地高辛合用时应动态监测地高辛血浓度 ,以免洋地黄中毒。由于ARB存在降压作用的平台反应 ,单一用药无法控制血压时 ,可联合应用利尿剂或钙拮抗剂。本文就ARB的药动学、降压治疗用药、联合用药 ,肝、肾功能不全时用药及药物相互作用作一综述     

真武汤联合厄贝沙坦、美托洛尔治疗心肾综合征患者的临床效果

目的研究真武汤联合厄贝沙坦、美托洛尔治疗心肾综合征患者的临床效果。方法选取2016年5月至2019年5月我院收治的100例心肾综合征患者为研究对象,根据入院顺序随机将其分为对照组与观察组,各50例。对照组给予厄贝沙坦、美托洛尔治疗,观察组在对照组基础上给予真武汤治疗。比较两组的临床疗效。结果治疗后,两组患者的Scr、BUN、BNP水平均降低,且观察组低于对照组(P<0.05)。观察组的治疗总有效率高于对照组(P<0.05)。治疗后,两组的CRP、IL-18、TNF-α水平均降低,且观察组低于对照组(P<0.05)。治疗后,两组的ET-1水平均降低,NO水平均升高,观察组优于对照组(P<0.05)。结论真武汤联合厄贝沙坦、美托洛尔治疗心肾综合征患者具有显著的协同作用,且能够降低患者的血清炎症因子水平,值得临床推广应用。     

PBPK modeling of irbesartan: incorporation of hepatic uptake

Physiological based pharmacokinetic (PBPK) modeling is now commonly used in drug development to integrate human or animal physiological data in order to predict pharmacokinetic profiles. The aim of this work was to construct and refine a PBPK model of irbesartan taking into account its active uptake via OATP1B1/B3 in order to predict more accurately its pharmacokinetic profile using Simcyp^®. The activity and expression of the human hepatocyte transporters OATP1B1 and OATP1B3 were studied. The relative activity factors (RAFs) for OATP1B1 and OATP1B3 transporters were calculated from intrinsic clearances obtained by concentration dependent uptake experiments in human hepatocytes and HEK overexpressing cells: RAF_1B1 using estrone‐3‐sulfate and pitavastatine clearances, and RAF_1B3 using cholecystokinine octapeptide (CCK‐8) clearances. The relative expression factor (REF) was calculated by comparing immunoblotting of hepatocytes (REF_HH) or tissues (REF_tissue) with those of overexpressing HEK cells for each transporter. These scaling factors were applied in a PBPK model of irbesartan using the Simcyp® simulator. Pharmacokinetic simulation using REF_HH (1.82 for OATP1B1, 8.03 for OATP1B3) as an extrapolation factor was the closest to the human clinical pharmacokinetic profile of irbesartan. These investigations show the importance of integrating the contribution of the active uptake of a drug in the liver to improve PBPK modeling. Copyright © 2015 John Wiley & Sons, Ltd.     

Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T₁ (AT₁) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.     

厄贝沙坦氢溴酸盐的毒理学和药效学研究

目的比较厄贝沙坦氢溴酸盐与厄贝沙坦的毒性和药效。方法采用无创血压测量比较了厄贝沙坦氢溴酸盐、厄贝沙坦对自发性高血压大鼠血压的影响。分别ip、ig给药,观察两种药物的半数致死量(LD50),对心率、呼吸以及动物自主活动的影响。结果自发性高血压大鼠的血压明显高于非自发性高血压大鼠,给予厄贝沙坦氢溴酸盐、厄贝沙坦后血压均降至正常水平,且两种药物的降压作用差异无显著性,但厄贝沙坦氢溴酸盐的药效持续时间更长。厄贝沙坦氢溴酸盐、厄贝沙坦对动物的呼吸、心率以及自主活动的影响无差异,但厄贝沙坦氢溴酸盐的LD50明显高于厄贝沙坦。结论厄贝沙坦氢溴酸盐具有和厄贝沙坦相同的降压作用,但是作用时间更长,安全性更高。     

重组人脑利钠肽联合厄贝沙坦对心肌梗死PCI术后患者疗效及HCY、IMA、Lp-PLA2影响

目的 观察重组人脑利钠肽（recombinant human brain natriuretic peptide,rhBNP）联合厄贝沙坦对急性心肌梗死（acutemyocardial infarction,AMI）经皮冠状动脉介入术（percutaneous coronary intervention,PCI）后患者疗效及对同型半胱氨酸（homocysteine,Hcy）、缺血修饰白蛋白（ischemia modified albumin,IMA）、脂蛋白相关磷脂酶A （2 lipoprotein-associated phospholipase A2,Lp-PLA2）影响。方法 选取2015年1月—2017年12月150例行PCI术成功的AMI患者,随机分为观察组（75例）和对照组（75例）,对照组患者术后予常规药物治疗和静脉注射rhBNP72 h;观察组在此基础上给予口服厄贝沙坦150 mg·d^-1。观察2组患者临床疗效、心肌酶学改变、心功能指标及不良反应情况;观察2组患者Hcy、IMA、Lp-PLA2改变。结果 观察组治疗后的临床治疗总有效率（89.33%）显著高于对照组（65.33%）（P<0.05）。与治疗前相比,治疗后2组患者体内CK和CK-MB峰值明显降低,观察组患者明显低于对照组（P<0.05）。与对照组比较,治疗后,观察组左心室功能参数改善明显（P<0.05）;血清HCY、IMA、Lp-PLA2含量下降更为明显（P<0.05）;心源性死亡、心肌二次梗死、再发心绞痛、心力衰竭人数较少,但不具有统计学差异;不良反应总数明显较低（P<0.05）。结论 rhBNP联合厄贝沙坦对PCI术后的AMI患者心肌具有保护作用,明显改善患者预后,可明显降低患者体内HCY、IMA、Lp-PLA2水平。