Influence of food on the bioavailability of diltiazem and two of its metabolites following the administration of conventional tablets and slow-release capsules

The influence of food on the bioavailability of a conventional tablet and of a slow-release capsule of diltiazem was investigated in two separate groups of 24 healthy volunteers in two open crossover studies. Diltiazem, as a conventional tablet (2 x 30 mg, first group) or as a slow-release capsule (120 mg SR, second group), was administered in a fasting condition and 30 min after a breakfast of 784 kcal (23 per cent proteins, 55 per cent lipids, and 22 per cent of carbohydrates). Multiple blood samples were withdrawn during the next 24 h and diltiazem, desmethyldiltiazem, and deacetyldiltiazem were assayed by HPLC. Neither the rate of absorption, assessed by the rate constant of absorption, the peak plasma concentration, and the time required to reach the peak, nor the amount of drug reaching the systemic circulation, assessed by the area under the plasma concentration time curve (AUC infinity) were influenced by food, and that independently of the formulation. Compared to the fasting experiment, food did not affect either the rate of formation or the AUC infinity of desmethyldiltiazem or deacetyldiltiazem. The results of the present study show that the relative bioavailability of the single dose of diltiazem administered as a slow-release capsule is significantly higher (69 per cent) than that estimated after the administration of diltiazem in a conventional tablet. It was concluded that food does not influence the bioavailability of diltiazem administered as a conventional tablet or as a slow-release formulation.     

An inhibitory effect of verapamil and diltiazem on the release of noradrenaline from ischaemic and reperfused hearts

We have investigated whether Ca2+ antagonists reduce the amount of noradrenaline lost from the myocardium during periods of ischaemia and reperfusion. Hearts obtained from adult, male normotensive Sprague Dawley, Wistar Kyoto and spontaneously hypertensive rats were perfused in the Langendorff mode at 37 degrees C before being made globally ischaemic for either 15, 30 or 60 min. Some of the hearts were reperfused, and in some ECG records were made. 90-min normothermic aerobic perfusion failed to cause a significant change in left ventricular noradrenaline content. In Sprague Dawley and spontaneously hypertensive, but not Wistar Kyoto rats, 15 min ischaemia followed by 1 min reperfusion caused a significant (P less than 0.05) loss of noradrenaline. Extending the ischemic episode to 60 min resulted in a further loss of noradrenaline (P less than 0.005) in the Sprague Dawley, Wistar Kyoto and spontaneously hypertensive hearts and this loss was exacerbated upon reperfusion. Neither dl verapamil (2.5 X 10(-8) to 1.2 X 10(-6) mol/l) nor diltiazem (0.25 to 1.25 X 10(-6) mol/l) caused any change in the noradrenaline content of the aerobically perfused hearts. (1.25 X 10(-1) to 1.2 X 10(-1) mol/l) verapamil abolished the release of noradrenaline caused by 15 min ischaemia and reduced the release caused by 60 min ischaemia and 15 min reperfusion. The dose-response curve for verapamil was bell-shaped and the activity resided in the l form. Diltiazem (1.25 X 10(-6) mol/l but not 2.5 X 10(-1) mol/l) also abolished the loss of noradrenaline caused by short periods of ischaemia and reperfusion.     

静脉注射地尔硫(卓)治疗先天性心脏病合并重度肺动脉高压

目的观察静脉注射地尔硫治疗先天性心脏病合并重度肺动脉高压的疗效。方法通过漂浮导管动态监测12例先天性心脏病合并重度肺动脉高压术后患者应用地尔硫(3~5μg.kg-1.min-1)持续静脉点滴,并记录应用地尔硫前、应用地尔硫后6h、试停呼吸机前、拔除气管插管后1h、24h的平均肺动脉压、平均动脉压、心率、每搏输出量、肺循环阻力、体循环阻力等指标的变化。结果12例患者无死亡,应用地尔硫后平均肺动脉压、肺循环阻力及心率显著降低,每搏输出量及平均动脉压显著增加,体循环阻力无明显改变,未发生肺高压危象。平均呼吸机辅助时间(88.7±50.1)h。结论静脉注射地尔硫能有效控制肺血管痉挛,从而降低肺动脉压,可用于治疗先天性心脏病合并重度肺动脉高压。     

A Comparison of the Effects of Diltiazem and Glyceryl Trinitrate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial

Purpose Anal fissure is a common problem affecting all age groups with an equal incidence in both sexes. Traditional surgical treatments, like manual anal dilatation or a sphincterotomy, effectively heal most fissures within a few weeks but such procedures may result in anal incontinence. In recent years, various medical therapies have been used for the treatment of chronic anal fissure without fear of incontinence. Methods Ninety patients with a symptomatic anal fissure were randomly divided into three groups. Group I was treated with 2% diltiazem ointment, Group II was treated with 0.2% glyceryl trinitrate (GTN) ointment, and Group III was kept as the control group. The improvement in the signs and symptoms, the time taken for healing, and side effects were recorded in each group. The patients were followed up monthly and then every 3 months for any recurrence of fissure. Comparative evaluations of the three groups regarding an improvement in symptoms, progress in healing, appearance of side effects, and recurrence were made using the Tukey HSD test. Results Diltiazem ointment was found to be superior regarding pain relief, fewer side effects, and late recurrence as compared with GTN ointment. Conclusion Diltiazem ointment (2%) and GTN ointment (0.2%) are both effective treatment modalities for chronic anal fissure, with diltiazem giving better patient outcome.     

Esmolol versus diltiazem in atrial fibrillation following coronary artery bypass graft surgery

SUMMARY

Purpose: Atrial fibrillation (AF) is the most common arrhythmic complication following coronary artery bypass graft surgery (CABG). The efficacy and safety of esmolol and diltiazem were compared in patients with post-CABG AF.

Methods: This study was a retrospective medical record review of consecutive patients with post-CABG AF >15?min in duration with a ventricular rate >110?b.p.m. who received either i.v. esmolol (n?=?59) or i.v. diltiazem (n?=?48) with or without concomitant digoxin therapy at a single university-affiliated teaching hospital. Treatment success was defined as either cardioversion to sinus rhythm or a reduction in the ventricular rate to <90?b.p.m. at 24?h after the start of therapy. Time to treatment success and the occurrence of adverse effects were considered secondary outcomes.

Results: A total of 107 patients with post-CABG AF were treated with i.v. esmolol (n?=?59) or i.v. diltiazem (n?=?48). The mean maximum dose of esmolol and diltiazem were 115?±?38?μg/kg/min and 11.2?±?3.5?mg/h, respectively. The average duration of the esmolol and diltiazem infusions were 19.3?±?8.5?h and 20.1?±?11.3?h, respectively. Based on the combined efficacy endpoint of cardioversion or ventricular rate control, esmolol was significantly more effective than diltiazem (90% vs 77%; p?=?0.038). Time to treatment success was significantly better for esmolol than diltiazem at all time points (1, 2,4,6,12, and 24?h post-treatment). The overall incidence of adverse effects was 44% with esmolol and 60% with diltiazem (p?=?0.04). Rates of drug discontinuance for adverse effects were significantly less for esmolol (20%) compared with diltiazem (38%) (p?=?0.04).

Conclusions: Esmolol is significantly more effective than diltiazem in the management of post-CABG AF. More patients converted to sinus rhythm with esmolol as compared to diltiazem. Esmolol was associated with fewer adverse effects than diltiazem, including adverse effects leading to drug discontinuance. Due to study design limitations (retrospective data collection), an adequately powered randomised, controlled trial is needed to confirm these preliminary findings.     

Development and in-vitro evaluation of modified release tablets including ethylcellulose microspheres loaded with diltiazem hydrochloride

In this study, development of modified release tablet formulations containing diltiazem hydrochloride-loaded microspheres to be taken once rather than two or three times a day was attempted. For this purpose, ethylcellulose microspheres were prepared by emulsion-solvent evaporation technique. The influence of emulsifier type and drug/polymer ratio on production yield, encapsulation efficiency, particle size, surface morphology and in-vitro release characteristics of the microspheres was evaluated. Suitable microspheres were selected and tabletted using different tabletting agents, Ludipress®, Cellactose®80, Flow-Lac®100 and excipients Compritol®888 ATO, Kollidon®SR. Tablets were evaluated from the perspective of physical and in-vitro drug release characteristics. It was seen that type and ratio of the excipients played an important role in the tabletting of the microspheres. As a result, two tablet formulations containing 180?mg diltiazem hydrochloride and using either Compritol®888 ATO or Kollidon®SR were designed successfully and maintained drug release for 24?h with zero order and Higuchi kinetics, respectively.     

Modulation of Drug Release Rate of Diltiazem–HCl from Hydrogel Matrices of Succinic Acid-Treated Ispaghula Husk

The feasibility of using succinic acid-treated ispaghula husk in matrix-based tablets of diltiazem–HCl was investigated. The sample prepared using 4:1 weight ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A 3² factorial design was employed to investigate the effect of amount of succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the percentage of the drug dissolved in 60, 300, and 480 min from the compressed tablets. The results of multiple linear regression analysis revealed that the significance of the amount of succinic acid-treated ispaghula husk was greater in magnitude than that of the amount of DCP in controlling the drug release. Acceptable batches were identified from a contour plot with constraints on the percentage drug released at the three sampling times. A mathematical model was also evolved to describe the entire dissolution profile. The results of F-test revealed that the Higuchi model fits well to the in vitro dissolution data. The tablets showed considerable radial and axial swelling in distilled water. Succinic acid-treated ispaghula husk can be used as an economical hydrophilic matrixing agent.     

美托洛尔、地尔硫卓及西地兰治疗快速型房颤的效果对比观察

目的比较美托洛尔、地尔硫卓及西地兰治疗快速型房颤的临床效果。方法选择102例快速型房颤患者,随机均分为3组,美托洛尔组使用美托洛尔注射液治疗,地尔硫卓组使用地尔硫卓注射液治疗,西地兰组使用西地兰注射液治疗,比较3种药物治疗后120min内不同时间点患者心室率的变化,并统计治疗前后患者血压变化情况。结果美托洛尔组治疗后5min患者心率即出现显著下降,低于治疗前（P〈0．05）,且显著低于地尔硫卓组和西地兰组（P〈0．05）．治疗后120min美托洛尔组收缩压和舒张压均显著高于地尔硫卓组（P〈0．05）。结论美托洛尔治疗快速型房颤起效迅速,对患者血压影响小,可以作为快速型房颤治疗的首先药物。     

芪参益气滴丸联合盐酸地尔硫（艹卓）治疗稳定型心绞痛的临床研究

目的 探讨芪参益气滴丸联合盐酸地尔硫（艹卓）片治疗稳定型心绞痛的临床疗效。方法 选择2020年2月—2020年9月在开封市中心医院治疗96例稳定型心绞痛患者,根据住院序号的奇偶性分成对照组（48例）和治疗组（48例）。对照组口服盐酸地尔硫（艹卓）片,30 mg/次,3次/d;治疗组在对照组基础上饭后口服芪参益气滴丸,0.5 g/次,3次/d。两组患者均经4周治疗。观察两组患者临床疗效,比较治疗前后两组患者心绞痛发作次数和持续时间,血清内皮细胞黏附分子1（VCAM-1）、活性氧自由基（ROS）、可溶性CD40配体（sCD40L）、转化生长因子β1（TGF-β1）、人白三烯B4（LTB4）和心肌营养素1（CT-1）水平,及SAQ、Gensini和GQOLI-74评分。结果 经治疗,对照组和治疗组总有效率分别为83.33%和97.92%,两组比较差异具有统计学意义（P<0.05）。经治疗,两组心绞痛发作次数、每次持续时间均显著减少（P<0.05）,且治疗组减少更明显（P<0.05）。治疗后,两组VCAM-1、ROS、sCD40L、LTB4、CT-1水平均明显降低,而TGF-β1明显升高（P<0.05）,且治疗组这些指标明显好于对照组（P<0.05）。治疗后,两组患者SAQ和GQOLI-74评分显著升高,而Gensini评分显著降低（P<0.05）,且治疗组明显好于对照组（P<0.05）。结论 芪参益气滴丸联合盐酸地尔硫（艹卓）片治疗稳定型心绞痛患者可有效改善患者胸痛症状,提高患者生活质量及改善冠状动脉受损情况,具有一定的临床推广应用价值。