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Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic model in Chinese miniature swine

Acta Pharmacologica Sinica 2007年第1期28卷 52-57页

作者： Jian-xun LIU~2 Zhen YU Xin-zhi LI Jian-hua FU Xiao-hong SHANG Ai-guo YAN Yue SHI Yan-lei MA Department of Pharmacology,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China Department of Pharmacology Xiyuan Hospital China Academy of Chinese Medical Sciences Beijing China

Aim:To develop a new model of myocardial ischemia in Chinese miniature swineand reevaluate the cardioprotective effects of ***:Myocardialischemia was induced by injecting self-embolus into the left anterior descending(LAD)coronary artery in qualified miniature ***(5 ***-1.d-1)wasorally administered to the swine by mixing into normal pig diet from 1 to 6 d afterself-embolus *** coronary angiography,30 point body surface electro-cardiogram(BS-ECG),hemodynamics,biochemistry,quantitative histology andpathohistology were determined 6 d after self-embolus ***:Embo-lization occurred in the LAD coronary artery of the Chinese miniature swine in-jected by *** were significant myocardial ischemia and largecardiac muscle infarction in the Chinese miniature swine,which were accompa-nied with increased BS-ECG,decreased hemodynamic indexes of the cardiac output,cardiac index,left cardiac work and left cardiac work index,and increased systemicvascular resistance *** analysis revealed myocardial degen-eration,necrosis,fibrosis,inflammatory cell infiltration and granulation tissuehyperblastosis(n=6).diltiazem diminished the extent of the LAD embolism,ame-liorated myocardial ischemia,improved the hemodynamic indexes,increased theplasma superoxide dismutase activity,decreased the plasma malondialdehydecontent,narrowed the myocardial ischemic area and weakened the pathohistologicaldamage in the cardiac muscle(n=6).Conclusion:Myocardial ischemia induced byinjecting self-embolus into the LAD coronary artery in Chinese miniature swine isquite close to clinical pathophysiological *** is effective toinhibit the myocardial ischemia and restore the heart function in this novel model.

关键词： myocardial ischemia diltiazem animal models Chinese miniature swine

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Quality of compounded topical 2% diltiazem hydrochloride formulations for anal fissure

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World Journal of Gastroenterology 2013年第34期19卷 5645-5650页

作者： Monil Shah Laura Sandler Vishwas Rai Charu Sharma Lakshmi Raghavan Ventrus Biosciences Inc. DermPathe Pharmaceuticals

AIM:To investigate the quality of topical 2%diltiazem formulations extemporaneously compounded by retail pharmacies openly offering drug-compounding ***:A participating healthcare professional wrote 12 prescriptions for compounded 2%diltiazem cream,with 2 refills allowed per *** 12sets of prescriptions were filled,at intervals of 1-2 wk between refills,at 12 different independent retail pharmacies that openly offer drug-compounding services in a major metropolitan *** 36 resultant preparations,provided as jars or tubes,were shipped,as soon as each was filled,at ambient temperature to the study core laboratory for high-performance liquid chromatography(HPLC)analysis,within 10 d of *** the HPLC analysis,8 different samples of the topical diltiazem,each approximately 1 g in weight,were taken from prespecified locations within each *** initiate the HPLC analysis,each sample was transferredto a 100 mL volumetric flask,to which methanol was *** HPLC analysis was conducted in accordance with the laboratory-validated method for diltiazem in cream,ointment,and gel *** main outcome measures were potency(percentage of label claim)and content uniformity of the compounded topical 2%diltiazem ***:Of the 36 prescriptions filled,30 were packaged in jars and 6 were packaged as *** prescriptions were specifically for cream formulations,but6 of the 12 pharmacies compounded 2%diltiazem as an ointment;for another pharmacy,which had inadequate labeling,the dosage form was *** United States Pharmacopoeia(USP)standard for potency is 90%-115%of label *** the 36 preparations,5(13.89%)were suprapotent and 13(36.11%)were *** suprapotent prescriptions ranged in potency from 117.2%to 128.5%of label claim,and the subpotent prescriptions ranged in potency from34.8%to 89.8%of label ***(38.9%)preparations lacked content uniformity according to the USP standard of 90%-110%pote

关键词： Anal fissure Pharmacy compounding Topical diltiazem Formulation potency Content uniformity

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Rhabdomyolysis induced by simvastatin-diltiazem interaction in unrecognized hypothyriodism

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Journal of Geriatric Cardiology 2010年第2期7卷 126-128页

作者： Ran Zhang Hai-Hong Ran Cai-Yi Lu Wei Gao Ya Huang Yu-Ling Gao Qiong-Xiang Yang Institute of Geriatric Cardiology Chinese PLA General HospitalBeijing 100853China Department of Geriatric Hematology Chinese PLA General HospitalBeijing 100853China

Simvastatin,a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor,is widely prescribed to patients with hypercholesteremia and its muscular toxicity has been widely *** metabolism of simvastatin depends on the enzymic activity of cytochrome P450 3A4 （CYP3A4） and inhibitors of CYP3A4 can result in clinical events by interacting with *** is a moderate inhibitor of CYP3A4,which is known to increase the serum concentration of *** we report a patient with unrecognized hypothyroidism who had been stable for more than one year on low-dose simvastatin therapy of hypercholesteremia and rhabdomyolysis occurred with the addition of *** is one of scanty reports of rhabdomyolysis induced by simvastatindiltiazem drug interaction,especially in hypothyroid *** case reminds the clinicians that although diltiazem as a moderate CYP3A4 inhibitor can be used cautiously with small doses of CYP3A4-dependent statius （eg,simvastatin）,these two commonly used drugs should be avoided in hypothyroid patient.

关键词： Simvastatin diltiazem drug-interaction rhabdomyolysis hypothyriedism

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Design and in vitro evaluation of controlled release alginate beads of diltiazem hydrochloride

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Asian Pacific Journal of Tropical Medicine 2009年第4期2卷 46-49页

作者： D.Nagasamy Venkatesh A.Kalaivani Kritika D.Kalro Lalitha Chintha James Tharani M.K.Samanta B.Suresh Department of Pharmaceutics JSS College of PharmacyOOTY-643001Tamil NaduIndia

Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compliance by prolonging dosing *** major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and *** has higher aqueous solubility and shorter elimination ***:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentration ***:The beads were characterized for its particle size,drug content and in vitro release studies. The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the *** results indicated there was an inverse relationship between the concentration of alginate and drug *** drug release was found to follow non-fickian diffusion obeying first order ***:The developed alginate microbeads offered a sustained release of diltiazem. Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.

关键词： Sodium alginate diltiazem Microbeads Ionotropic gelation technique Peppa’s model

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The effects of diltiazem in renal transplantation patients treated with cyclosporine A

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The Journal of Biomedical Research 2010年第4期24卷 317-323页

作者： Wujun Xue Yong Song Puxun Tian Xiaoming Ding Xiaoming Pan Hang Yan Jun Hou Xinshun Feng Heli Xiang Xiaohui Tian Department of Renal Transplant Center of Nephropathy the First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China

Objective： To investigate the effects of diltiazem and cyclosporine A （CsA） combination therapy on protecting the kidney, promoting graft functioning and improving post-transplanted kidney recovery. Methods： The blood con- centrations of CsA, the condition of the post-transplant kidney, the rate of acute rejection （AR）, as well as hepatic and renal toxicity in 636 cases of renal transplant recipients were determined after being treated by CsA, with or without diltiazem. Results： Compared with the control group which received CsA, mycophenolate mofetil （MMF） and prednisolone （Pred） but lacked diltiazem, the group receiving these agents together with diltiazem required reduced dosage of CsA （P 〈 0.01）, while blood concentrations of CsA were significantly increased （P 〈 0.01）; the recovery time of graft function was reduced from （6.2± 1.5） d to （3.9± 1.4） d （P 〈 0.01）, and the rate of AR was decreased from 13.2% to 7.9% （P 〈 0.01）. Conclusion： In renal transplantation patients treated with CsA and diltiazem, blood concentrations of CsA were increased while the dosage was decreased. This efficient combination therapy reduced patients economic burden, at the same time retained kidney function, promoted graft function recovery and decreased hepatic and renal toxicity and the rate of AR.

关键词： transplant/kidney diltiazem cyclosporine A

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diltiazem used as a tacrolimus-sparing agent for treatment of pediatric patients with refractory nephrotic syndrome: a case report and retrospective analysis

Diltiazem used as a tacrolimus-sparing agent for treatment o...

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第八届全国治疗药物监测学术年会

作者： Ya-Hui Hu Jie-Yu Sun Hong-Li Guo Ze-Jun Xu Xia Jing Fang Sun Hui-Lei Guo Feng Chen Jing Xu Department of Pharmacy Children’s Hospital of Nanjing Medical University

The 2012 Kidney Disease Improving Global Outcomes(KDIGO) guidelines recommended calcineurin inhibitor tacrolimus to be used to treat several types of nephrotic syndrome(NS) in children and adults, such as steroid-resistant nephrotic syndrome(SRNS), steroid-dependent NS and frequently relapsing idiopathic membranous nephropathy. Owing to its narrow therapeutic window and chronic nephrotoxicity,tacrolimus drug level should be closely therapeutically monitored. Furthermore,due to immunosuppressant-associated toxicities aggravate immune-mediated nephron injury and side effects, low dosing strategies have been increasingly adopted. Based on its metabolic elimination pathway, CYP3A5 genotype and drug-drug interaction will profoundly impact the systemic exposure to tacrolimus after medication. We report here the case of a Chineseboy, aged 5 years, who was diagnosed with refractory nephrotic syndrome(RNS) and was given tacrolimus. The tacrolimus dose was tailored according to the therapeutic concentration window, CYP3A5 genotype, and minimal dosage strategy. More importantly, in combination with corticosteroids and tacrolimus, diltiazem was used as a tacrolimus-sparing agent for the *** also retrospectively reviewed the coadministered therapy records from 2016 to 2018 at our hospital to evaluate the spring effect of diltiazem. diltiazem induced an average increase of tacrolimus trough concentration(C) by 86.5%, irrespective of the CYP3A5 genotype. Tacrolimus maintenance dose ranged from 0.058 to 0.091 mg/kg/d, and the monitored mean C reached to 4.6 μg/L. Serum albumin, total cholesterol, triglyceride, and urine protein of the pediatric patients were within the normal ranges after treatment, and nonephrotoxicity was observed. Additionally,regular dose of diltiazem was well ***: CYP3A5 genotype screening is informative to tailor the tacrolimus dosage. diltiazem was proved to be an effective tacrolimus-sparing agent for pediatric RNS treatment. Long-

关键词： Tacrolimus diltiazem Refractory nephrotic syndrome Drug-drug Interaction CYP3A5 Genetic polymorphism Therapeutic drug monitoring

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A Brief Review of a Common Clinical Question: Intravenous diltiazem or Metoprolol for Atrial Fibrillation with Rapid Ventricular Response?

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World Journal of Cardiovascular Diseases 2023年第9期13卷 550-555页

作者： Zachary Visinoni Neeladri Misra Daniel Jurewitz Department of Graduate Medical Education Internal Medicine Residency Sutter Roseville Medical Center Roseville USA Sutter Medical Group Roseville USA Sutter Medical Group Cardiology Roseville USA

Two classes of rate controlling medications—beta blockers (BBs) and non- dihydropyridine calcium channel blockers (CCBs)—are given to patients who present with atrial fibrillation (AF) with rapid ventricular response (RVR). Both are Class I recommendations from the American Heart Association (AHA), American College of Cardiology (ACC), and Heart Rhythm Society (HRS) for the management of AF with RVR. Multiple studies support the view that diltiazem is more effective than metoprolol, even though data from the AFFIRM trial suggests BBs are more frequently used. CCBs are generally avoided in AF with RVR patients who have concomitant heart failure with reduced ejection fraction (HFrEF) for concern of triggering decompensation. However, some recent studies indicate this idea may be unfounded. The aim of this article is to compare the efficacy of diltiazem and metoprolol for rate control in AF with RVR and examine the use of diltiazem in patients with both AF with RVR and HFrEF.

关键词： Atrial Fibrillation Rapid Ventricular Response diltiazem Metoprolol Heart Failure with Reduced Ejection Fraction

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Effect of calcium and diltiazem on phenylhydrazine-induced oxidative injury in goat erythrocytes

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Health 2010年第10期2卷 1221-1225页

作者： Kaushik Das Jharna Bhattacharyya 不详

Lipid peroxidation, hemolysis and thiol contents were studied in intact goat erythrocytes exposed to phenylhydrazine. An increase in lipid peroxidation, hemolysis and thiol content was observed after phenylhydrazine treatment of erythrocyte. Extracellular Ca2+ potentiates the phenylhydrazine-induced lipid peroxidation and hemoly- sis of erythrocytes significantly. Ca2+ does not influence much the thiol content of phenylhydrazine treated erythrocytes. No effect of Ca2+ on control lipid peroxidation, hemolysis and thiol contents of erythrocytes was observed. diltiazem and EDTA inhibited the increased responses of lipid peroxidation and hemolysis due to Ca2+. However the thiol content was not much influenced by either diltiazem or EDTA. The results suggest that oxidative damage of erythrocyte caused by phenyl hydrazine could be prevented by calcium channel antagonist, diltiazem, which may act as antioxidant also.

关键词： Ca2+ diltiazem Erythrocyte Free Radical Lipid Peroxidation Phenylhydrazine

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Simultaneous determination of isosorbide mononitrate,metoprolol tartrate and diltiazem hydrochloride by micellar liquid chromatography

Simultaneous determination of isosorbide mononitrate,metopro...

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甘肃省化学会第二十八届年会暨第十届中学化学教学经验交流会

作者： Li Ning Dong Yuming School of Pharmacy Lanzhou University

In clinical,p-blockers(e.g.,metoprolol tartrate(ME)),calcium channel blockers(e.g.,diltiazem hydrochloride(DL)) and nitrates(e.g.,isosorbide mononitrate(ISMN)) have been used in cardiovascular diseases and ME,DL and ISMN(Fig 1) are common drugs to cure *** order to improve the curative effect,the angina is treated by drug combinations in general[1].In order to design a personal treatment plan for individuals,it is necessary to establish a sensitive and fast analytical method to determine these analytes in angina patients’ serum.

关键词： Micellar liquid chromatography metoprolol isosorbide mononitrate diltiazem

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Nifedipine and diltiazem Protect L-VDCC-/-H9c2 Cells against Hypoxia/Reoxygenation Injury via Regulating the Expression of Cyclooxygenase-2

Nifedipine and Diltiazem Protect L-VDCC-/-H9c2 Cells against...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Man Liu Ganggang Shi Department of Pharmacology Shantou University Medical College

Restoration of the coronary blood flow of ischemic heart induces additional cardiac damage and complications,such as inflammation,oxidative stress and apoptosis,named as myocardial ischemia/reperfusion（I/R） injury,also called hypoxia/reoxygenation（H/R） *** previous work has indicated that nifedipine and diltiazem can protect myocardium against I/R injury through blocking L-type voltage-dependent calcium channel（L-VDCC）.However,it has been reported that nifedipine and diltiazem can also reduce I/R injury in a L-VDCC-independent way,which has been confirmed by our ***-2（COX-2）,which has been reported to be related to H/R injury,is a key enzyme for the production of *** work is to study whether or not nifedipine and diltiazem can regulate the expression of COX-2 to alleviate cardiomyocytes H/R injury in a L-VDCC-independent *** & Methods L-VDCCH9 c2 cells were divided into:CON,H/R,H/R+DMSO,H/R+nifedipine,H/R+diltiazem,H/R+NS-398（selective inhibitor of COX-2） *** was achieved by placing the cells on a hypoxia chamber,containing 94% N and 5% CO1% O at 37℃ to mimic *** was achieved by exposing cell to normal medium and room air with atmosphere containing 5% CO,95% O at 37 ℃.Nifdepine,diltiazem or NS-398 was added to the changed medium during H/R *** of COX-2 mRNA was detected by Quantitative PCR. COX-2 and cleaved-caspase3 protein expression was detected by Western ***6（IL-6） concentration,malondialdehyde（MDA） content and superoxide dismutase（SOD） activity were measured by relative *** apoptotic cells were measured by Annexin-V FITC/*** were analyzed using one-way ANOVA followed by Tukey's *** In H/R group,COX-2 mRNA and protein expression were up-regulated;IL-6 concentration,MDA content,cleaved-caspase3 protein expression and early apoptotic cells were increased and SOD activity group was decreased compared with CON *** H/R+NS-398 group,I

关键词： nifedipine diltiazem L-VDCC-/-H9c2 cells hypoxia/reoxygenation COX-2

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