Interaction of bisoprolol with cimetidine and rifampicin

Summary In 6 healthy volunteers the pharmacokinetics of bisoprolol under steady-state conditions was investigated over three consecutive phases: over 7 days of 10 mg of bisoprolol once daily per os, 7 days of 10 mg of bisoprolol once daily plus 400 mg of cimetidine t.i.d. and 14 days of 10 mg of bisoprolol and 600 mg of rifampicin once daily with adequate intervals free of medication. After therapy with bisoprolol alone peak plasma levels (C _max ^ss ) of the beta-blocker were 55.5±6.4 ng/ml (x±SEM), area under the plasma level-time curve (AUC) was 597±70 ng/ml.h, total body clearance (CL) 15.8±1.8 l/h and elimination half-lives (t_1/2) 10.1±1.2 h. Cimetidine did not cause any significant changes in the pharmacokinetics of bisoprolol. Co-administration of rifampicin resulted in a decrease in C _max ^ss (43.0±6.9 ng/ml), AUC (397±54 ng/ml·h) and t_1/2 (6.2±0.4 h). Accordingly, total body clearance increased to 23.8±2.51/h (p<0.05). In conclusion bisoprolol showed a statistically significant but probably clinically not important interaction with the enzyme-inducing drug rifampicin, but not with the enzyme inhibitor cimetidine.     

Effects of trimetazidine in combination with bisoprolol in patients with chronic heart failure and concomitant chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis

Background:To the best of our knowledge, there is no study that has conducted a review investigating the clinical efficacy and safety of bisoprolol combined with trimetazidine on chronic heart failure (CHF) patients with chronic obstructive pulmonary disease (COPD). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of bisoprolol combined with trimetazidine on CHF patients with COPD.Methods:Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in April 2021 by 2 independent reviewers. For search on PubMed, the following search terms will be used: “trimetazidine, bisoprolol, chronic heart failure, chronic obstructive pulmonary disease.” In order to achieve a consistency of extracted items, the data extractors will extract data from a sample of eligible studies. The outcomes include all-cause mortality and hospitalization for cardiac or/and respiratory causes; left ventricular structure and function; and functional scores. Review Manager software (v 5.4; Cochrane Collaboration) will be used for the meta-analysis. Two independent reviewers will assess the risk of bias of the included studies at study level. Any disagreements will be discussed and resolved in discussion with a third reviewer.Results:The results of our review will be reported strictly following the PRISMA criteria.Conclusions:The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.OSF registration number:10.17605/OSF.IO/ZWPRB.     

比索洛尔对持续性非瓣膜性心房颤动患者心房结构重构的影响

目的观察比索洛尔对持续性非瓣膜性心房颤动患者心房结构重构及C反应蛋白(CRP)的影响,并探讨其可能关系。方法将85例持续性非瓣膜性心房颤动患者,分为比索洛尔组(48例)和地高辛组(37例),随访观察(9.8±1.3)个月,治疗前后检测CRP和超声心动图观察左心房结构变化。结果比索洛尔组治疗后左心房内径(41.8±4.2)mmvs(39.7±5.3)mm,CRP 3.9 mg/Lvs3.5 mg/L,均较治疗前明显下降,差异有统计学意义(P<0.01),而地高辛组治疗前后左心房内径(41.8±4.6)mmvs(42.3±5.2)mm,CRP 3.8 mg/Lvs3.5 mg/L,差异无统计学意义(P>0.05)。比索洛尔组的左心房内径和CRP下降幅度与地高辛组比较,差异有统计学意义(P<0.01)。相关分析显示,左心房内径变化与CRP变化呈显著正相关(r=0.218,P=0.045)。结论比索洛尔可改善持续性非瓣膜性心房颤动患者的心房结构重构,并减轻炎性反应。     

Effect of Cibenzoline,a Class Ia Antiarrhythmic Agent,on Left Ventricular Diastolic Function in Hypertrophic Cardiomyopathy

We aimed to investigate whether the improvement of left ventricular (LV) diastolic function by cibenzoline, a class Ia antiarrhythmic drug, in hypertrophic obstructive cardiomyopathy (HOCM) is due to LV afterload reduction or a primary lusitropic effect on LV. Twenty-three patients with hypertrophic cardiomyopathy (11; HOCM, 12; non-obstructive HCM; HNCM) were examined. Pulsed-wave Doppler, color M-mode and tissue Doppler echocardiography were performed before and 90 minutes after oral administration of cibenzoline (300 mg), and were compared with a treatment of bisoprolol (5 mg/day, 10 days). Early (E) and late diastolic LV inflow velocity, E flow propagation velocity (FPV) and early diastolic mitral annulus velocity (Ea) were measured. E/FPV and E/Ea were calculated as indices of LV filling pressure. LV outflow pressure gradients estimated using continuous-wave Doppler in HOCM markedly decreased after cibenzoline (83 +/- 42 to 40 +/- 33 mmHg, p < 0.005) and bisoprolol (44 +/- 40 mmHg, p < 0.005). Following cibenzoline, E/FPV and E/Ea were significantly decreased in both HOCM (1.75 +/- 0.53 to 1.32 +/- 0.28, p < 0.05, 18.9 +/- 6.2 to 14.8 +/- 5.0, p < 0.05, respectively) and HNCM (1.75 +/- 0.58 to 1.41 +/- 0.73, p< 0.05, 13.0 +/- 4.3 to 9.7 +/- 3.6, p< 0.01, respectively). Those in HNCM did not change by bisoprolol. Cibenzoline improved LV diastolic function in HCM, whereas bisoprolol did not affect it. Thus, the primary lusitropic effect of cibenzoline rather than LV after load reduction might have contributed to the improvement of diastolic function in HOCM.     

卡维地洛、比索洛尔、哌唑嗪对SHR心肌成纤维细胞增殖作用的对比研究

目的 观察卡维地洛(carvedilol)、比索洛尔(bisoprolol)、哌唑嗪(prazosin)对培养的SHR和Wistar大鼠心肌成纤维细胞(CFs)增殖的影响。方法 采用胰酶消化法培养CFs，用^3H—TdR法、MTT比色法分别观察carvedilol、bisolol、prazosin干预下CFs的增殖情况。结果 SHR、Wistar大鼠CFs^3H-TdR掺入及OD值随carvedilol浓度的增加而减低，呈剂量和时间依赖性。10^-5mo1／L carvedilol分别干预SHR和Wistar大鼠CFs72h其h其^H-TdR掺入分别减低52．1％和47．5％，OD值分别减低41．5％和35．3％，bisolol(10^-8mo1／L一10^-5mol／L)和przosin(10^-8mol／L一10^-5mol／L)则无此作用。结论 Carvedilol抑制心肌成纤维细胞增殖，并呈浓度及时间依赖性，高血压时，CFs对Carvedilol更为敏感。而Bisoprolol和Prazosin则对CFs细胞增殖无影响。     

比索洛尔提高心力衰竭大鼠心肌SERCA2a活性

目的观察比索洛尔对心力衰竭大鼠心肌肌浆网钙ATP酶2a(SERCA2a)活性的影响。方法腹腔注射阿霉素建立大鼠心力衰竭模型。实验分为对照组、假手术组、模型组、比索洛尔组、卡托普利组和比索洛尔+卡托普利组。检测心功能指标;ELISA法检测血浆脑钠肽水平;茎环状引物实时定量PCR检测心肌miR-25-3p表达水平;Western blot检测心肌SERCA2a和受磷蛋白(PLB)表达水平;定磷法测定心肌SERCA2a活性。结果与对照组比较,模型组大鼠心功能明显减退(P0.01),血浆脑钠肽水平和心肌miR-25-3p表达水平明显升高(P0.01),SERCA2a和PLB表达水平、SERCA2a/PLB比值和SERCA2a活性明显降低(P0.01);与模型组比较,比索洛尔组、卡托普利组和比索洛尔+卡托普利组大鼠心功能明显改善(P0.01),血浆脑钠肽水平和心肌miR-25-3p表达水平明显降低(P0.01),SERCA2a和PLB表达水平明显升高(P0.01);比索洛尔组和比索洛尔+卡托普利组SERCA2a/PLB比值和SERCA2a活性明显高于模型组(P0.05)。结论比索洛尔可以下调心肌miR-25-3p表达水平,提高SERCA2a和PLB表达水平,增强SERCA2a活性。     

IL －33／ST2信号通路在比索洛尔治疗舒张性心力衰竭中的作用

目的：观察IL－33／ST2信号通路在比索洛尔治疗舒张性心力衰竭（ DHF）中的作用。方法24只舒张性心力衰竭老鼠随机分为对照组（n＝12）及比索洛尔组（n＝12）,分别用蒸馏水及比索洛尔溶液治疗,疗程6周。观察2组的左室压力、左室充盈时间（ LVFT）、左室舒张压、等容收缩期左心室内压最大上升速率及心肌细胞ST2蛋白及血清肿瘤坏死因子（ TNF－α）的浓度。结果比索洛尔组小鼠左室收缩压、左心室平均压均显著低于对照组（P＜0.05）,但2组左室舒张压差异无统计学意义（ P＞0.05）。比索洛尔组等容收缩期左心室内压最大上升速率显著高于对照组（ P＜0.05）;等容舒张期左心室内压最大下降速率显著低于对照组（P＜0.05）,而左室充盈时间2组差异无统计学意义（P＞0.05）。比索洛尔组IL－33蛋白表达显著降低（ P＜0.05）,但ST2表达量和血清中TNF－α浓度2组差异均无统计学意义（ P＞0.05）。结论比索洛尔可有效降低舒张性心力衰竭小鼠的左室血压,改善左心室顺应性,其机制可能与心肌细胞内IL－33蛋白表达量显著减少有关。     

厄贝沙坦氢氯噻嗪联合富马酸比索洛尔对青年高血压的实效性研究

目的：观察并探讨厄贝沙坦氢氯噻嗪（IH ）联合富马酸比索洛尔（BIS ）对青年高血压的治疗价值。方法选择自2012年9月至2015年2月在该院治疗的青年高血压患者96例,按照随机分组法将96例患者分为观察组和对照组各48例。对照组在常规治疗的基础上给予IH治疗,观察组在对照组基础上加用BIS治疗。治疗前、后监测两组患者的收缩压（SBP）、舒张压（DBP）和心率（HR）,左心室舒张末期内径（LVEDD）、E峰和左心室射血分数（LVEF）,并在治疗后根据血压改善情况对综合疗效进行评价。结果两组患者治疗前SBP、DBP、HR、LVEDD、E峰和LVEF比较,差异无统计学意义（P＞0．05）;治疗后观察组SBP、DBP和HR分别为（116．4±11．8）mm Hg、（85．3±6．7）mm Hg和（65．2±7．1）次／分,对照组为（132．8±14．6）mm Hg、（96．3±6．2）mm Hg和（75．2±8．1）次／分,两组比较差异有统计学意义（P＜0．05）;治疗后观察组患者LVEDD明显低于对照组,而E峰和LVEF明显高于对照组（P＜0．05）;治疗后,观察组总有效率为95．8％（46／48）,对照组总有效率为75．0％（36／48）,两组比较差异有统计学意义（P＜0．05）。结论 IH联合BIS治疗能明显改善青年高血压患者的血压水平,疗效显著,是青年高血压安全有效的治疗方法。     

拉西地平联合比索洛尔治疗老年高血压的疗效观察

目的观察拉西地平与比索洛尔联合治疗老年高血压的临床疗效。方法用药前停服其他任何降压药物1周,给予口服拉西地平4mg,1次/日,比索洛尔5mg,1次/日。两种药物根据血压情况可调整剂量至:拉西地平8毫克/日,比索洛尔10毫克/日,口服,直至血压降至正常。用药时间均连续4周。结果治疗后收缩压(140.1±12.6)mm Hg、舒张压(91.2±5.4)mm Hg、心率(63.2±5.7)次/分与治疗前(163.3±18.7)mm Hg、(108.2±7.6)mm Hg、(74.3±8.3)次/分比较差异有统计学意义(P<0.01);空腹血葡萄糖、胆固醇、三酰甘油、低密度脂蛋白胆固醇、丙氨酸氨基转移酶、血清肌酐治疗后与治疗前比较差异无统计学意义(P>0.05)。结论拉西地平与比索洛尔联合应用治疗老年高血压,在控制收缩压、舒张压、心率方面能发挥各自优势,起到协同作用。     

Bisoprolol inhibits sodium current in ventricular myocytes of rats with diastolic heart failure

1. Changes in sodium currents (I(Na)) in heart failure contribute to cardiac electrophysiological alterations and, thereby, to ventricular arrhythmias. Bisoprolol has anti-arrhythmic effects, but its direct effect on I(Na) in cardiac cells remains unclear. Accordingly, in the present study we investigated the effects of bisoprolol on ventricular I(Na) in diastolic heart failure (DHF) and normal rats. 2. The DHF model was produced by abdominal aortic coarctation for 4 weeks and single ventricular myocytes were isolated by enzymatic dissociation. The electrophysiological actions of bisoprolol on I(Na) currents were investigated using a whole-cell patch-clamp technique. 3. The membrane capacitance of rats in the DHF group was significantly greater than that of the control group and the current-voltage curve was simultaneously shifted downward. Bisoprolol concentration-dependently decreased I(Na) in ventricular myocytes of both groups (at -45 mV), with IC(50) values of 19.53 +/- 0.06 and 40.78 +/- 0.03 micromol/L in the control and DHF groups, respectively. 4. In both groups, the current-voltage curves were shifted upwards, whereas activation potentials, peak currents and reversal potentials showed no significant changes. At -45 mV, the descent ratio of current densities in the DHF group was lower than that of the control group. In both groups, inactivation curves were shifted to more negative potentials, but activation curves and recovery curves were not altered. Changes in the half-inactivation voltage, V(0.5), and the slope of the inactivation curve, S, were similar for both groups. 5. In conclusion, bisoprolol concentration-dependently decreases I(Na) in ventricular myocytes of DHF and normal rats, which could be responsible, at least in part, for its anti-arrhythmic effects.