Dihydropyridine Calcium Antagonist Research Articles

Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability.

PurposeNimodipine (NMP) is a clinical dihydropyridine calcium antagonist. However, the clinical application of NMP is limited by poor water solubility and low oral bioavailability. To overcome these drawbacks, this study designed optimal NMP-incorporated nanostructured lipid carriers (NLCs).MethodsHigh-pressure homogenization was successfully applied to prepare NMP-NLC, and the nanoparticle morphology was observed by a transmission electron microscope. The existence form of NMP in NMP-NLC was investigated by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy, respectively. The in vitro release study was performed by the dialysis method, and in vivo studies including in situ intestinal perfusion and pharmacokinetics were investigated in rats with NMP detected by high-performance liquid chromatography.ResultsThe obtained NMP-NLC shared a spherical shape of ~70 nm with a smooth surface and high encapsulation efficiency of 86.8%±2.1%. Spectroscopy indicated that the drug was in an amorphous state. The NMP-NLC exhibited a sustained release and diverse release profiles under different release medium, which mimicked the physiological environment. Moreover, an in situ intestinal perfusion experiment revealed that NMP-NLC could be mainly absorbed by the small intestine. Remarkable improvements in Cmax and AUC0–∞ from NMP-NLC were obtained from pharmacokinetic experiments, and the relative bioavailability of NMP-loaded nanostructured lipid systems was 160.96% relative to NMP suspensions.ConclusionCollectively, the NLCs significantly enhanced the oral bioavailability of NMP and might provide a promising nanoplatform for hydrophobic drug delivery.

Antihypertension drugs in prevention of cognition disorder and dementia: focus on calcium channel blockers and diuretics

Arterial hypertension is associated with elevated risk of cognition decline and vascular dementia development, as the Alzheimer disease development. Therefore, antihypertension therapy might be of preventive value. The review is focused on literary data that witness on, despite controversial, evidence of cerebroprotective action of the range of antihypertension medications. Especially, dihydropyridine calcium antagonists, diuretics and some blockers of renin-angiotensin-aldosterone system. These act not only via blood pressure decrease, but due to additional specific neuroprotective mechanisms. This makes it to consider calcium antagonists and diuretics as a major component of systemic hypertension management, incl. elderly and senile patients, aiming to prevent cognition decline and dementia of various types development.Nitrendipine, among the calcium channels antagonists, and indapamide among diuretics have acquired the broadest evidence that points on their cerebroprotective properties.

Lactobacillus plantarum IS-10506 probiotic administration increases amlodipine absorption in a rabbit model.

ObjectiveProbiotics are beneficial in human health. In this study, we investigated the effect of probiotics on absorption of amlodipine, a dihydropyridine calcium antagonist used in the treatment of angina and hypertension, in a rabbit model.MethodsLactobacillus plantarum IS-10506 probiotic was administered for 14 days to male New Zealand rabbits. Blood samples were collected before and after probiotic supplementation. Amlodipine (10 mg) was then administered to all groups. Blood samples from a marginal vein were withdrawn at 5, 15, 30, 60, and 120 minutes to determine amlodipine concentrations in rabbit plasma.ResultsAmlodipine concentrations in the L. plantarum IS-10506 group were 4.95 ± 1.22, 8.71 ± 0.69, and 12.48 ± 2.53 ng/ml, and those in the control group were 1.69 ± 0.31, 3.89 ± 1.23, and 7.17 ± 1.85 ng/ml at 30, 60, and 120 minutes, respectively after administration of amlodipine. Amlodipine concentrations in the L. plantarum IS-10506 group were significantly higher than those in the control group at 30, 60, and 120 minutes after amlodipine administration.ConclusionOur results suggested that supplementation of L. plantarum IS-10506 significantly increases amlodipine plasma concentrations in rabbits.

Когнитивные нарушения и деменция у больных пожилого возраста с артериальной гипертонией

The article describes the definition of dementia, its diagnostic criteria, classification. Differences in the pathogenesis and clinical manifestations of different types of dementia are considered. The issues of interrelation of arterial hypertension and the risk of development of cognitive disorders and dementia in old and very old people are discussed in detail. Data on the effect of antihypertensive drugs of different groups on the risk of dementia and the state of cognitive functions are presented. The evidence base of dihydropyridine calcium antagonist amlodipine and thiazide-like diuretic indapamide-retard is discussed with respect to the prevention of dementia and cognitive decline and their beneficial effect on cognitive function in patients with arterial hypertension.

Pharmacokinetics and drug-drug interaction between enalapril, enalaprilat and felodipine extended release (ER) in healthy subjects.

Since angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have complimentary mechanisms of action, enalapril, an ACE inhibitor, is used in combination with felodipine, a vascular selective dihydropyridine calcium antagonist, for the treatment of hypertension. The present study was designed to investigate the possible drug-drug interaction between these two agents in Chinese healthy subjects. A randomized, open-label, multiple-dose, 3-treatment, 3-period, 6-sequence cross-over study enrolling 12 healthy subjects (six male and six female subjects) was performed. Plasma pharmacokinetic studies were performed after 5 mg of enalapril and 5 mg of felodipine were administered alone or concomitantly twice per day for six days, and once in the morning of day seven. All 12 healthy subjects (mean [SD] age, 24.3 [2.8] years; body weight, 57.3 [5.7] kg; height, 163.2 [5.2] cm) completed all scheduled pharmacokinetic studies. Geometric mean ratios (with 90% CIs) of AUCτ,ss and Cmax,ss for enalapril administered concomitantly with felodipine vs. enalapril administered alone were 1.025 (0.80-1.25) and 1.065 (0.70-1.43), respectively. Geometric mean ratios (with 90% CIs) of AUCτ,ss and Cmax,ss for felodipine administered concomitantly with enalapril vs. felodipine administered alone were 1.14 (0.97-1.31) and 0.80 (0.65-0.95), respectively. There were no severe or serious drug-related adverse events observed during the study. Our results revealed that the co-administration of enalapril and felodipine affected the pharmacokinetics of felodipine, but not that of enalapril. Although the difference in PK parameters was statistically significant, its clinical significance may be limited, considering safety profile observed in the present study.

Adherence to Treatment, Safety, Tolerance, and Effectiveness of Perindopril/Amlodipine Fixed-Dose Combination in Greek Patients with Hypertension and Stable Coronary Artery Disease: A Pan-Hellenic Prospective Observational Study of Daily Clinical Practice.

Initiation of antihypertensive therapy with a two-drug fixed-dose combination (FDC) in a single tablet may be recommended in patients at high risk of cardiovascular events to improve adherence and effectiveness. Preferred combinations include an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium antagonist. This study assessed adherence to and the safety, tolerance, and effectiveness of the perindopril/amlodipine FDC in Greek patients with hypertension and stable coronary artery disease (CAD) over a 4-month period. A total of 1907 patients with hypertension and CAD (59.1% males) who had recently (≤2weeks) commenced treatment with the perindopril/amlodipine FDC (5/5, 5/10, 10/5, or 10/10mg) were studied at baseline and at 1 and 4months. Adherence to treatment was assessed with the Morisky Medication-taking Adherence Scale (MMAS). Seven patients (0.4%) did not attend the scheduled visits. In total, 1607 (84.6%) patients received a constant treatment dose throughout the study. High adherence (MMAS score=0) was reported by 1592 (83.6%), 1628 (85.7%), and 1477 (77.7%) patients at the second and thethird visit and at both visits, respectively. Adverse reactions were reported by only 13 (0.7%) patients, were all minor, and did not result in treatment discontinuation. Office blood pressure (BP) was significantly decreased at the third visit (130.8±8.4/78.2±6.4mmHg) compared with baseline (156.5±15.0/89.9±9.6mmHg; p<0.001), regardless of previous antihypertensive treatment. Patients with grade 1, 2, and 3 hypertension at baseline showed a reduction in BP of 19.3/9.4, 31.5/13.5, and 47.8/22.2mmHg, respectively (p<0.001). Uncontrolled hypertension (≥140/90mmHg) was notably reduced from 90.3% at baseline to 18.5% at the third visit. The perindopril/amlodipine FDC is characterized by high adherence and effectiveness, regardless of previous treatment. Degree of BP reduction was related to baseline BP levels. Clinical trials registration number (Protocol Number): IC4 - 05985 - 011 - GRC.

Dihydropyridine calcium antagonists: conscious choice

This article contains information concerning the aspects of pharmacokinetics and pharmacodynamics of dihydropyridine calcium antagonists. The authors have discussed the evidence-based amlodipine treatment of arterial hypertension, ischemic heart disease and chronic heart failure. The authors present the comparison of the efficacy, safety and application characteristics of the different dihydropyridine calcium antagonists that can be used in specific clinical cases.

Дигидропиридиновые антагонисты кальция: осознанный выбор

This article contains information concerning the aspects of pharmacokinetics and pharmacodynamics of dihydropyridine calcium antagonists. The authors have discussed the evidence-based amlodipine treatment of arterial hypertension, ischemic heart disease and chronic heart failure. The authors present the comparison of the efficacy, safety and application characteristics of the different dihydropyridine calcium antagonists that can be used in specific clinical cases.

Impact of the introduction of mandatory generic substitution in South Africa: private sector sales of generic and originator medicines for chronic diseases.

To assess the impact of mandatory offer of generic substitution, introduced in South Africa in May 2003, on private sector sales of generic and originator medicines for chronic diseases. Private sector sales data (June 2001 to May 2005) were obtained from IMS Health for proton pump inhibitors (PPIs; ATC code A02BC), HMG-CoA reductase inhibitors (statins; C10AA), dihydropyridine calcium antagonists (C08CA), angiotensin-converting enzyme inhibitors (ACE-I; C09AA) and selective serotonin reuptake inhibitors (SSRIs; N06AB). Monthly sales were expressed as defined daily doses per 1000 insured population per month (DDD/TIM). Interrupted time-series models were used to estimate the changes in slope and level of medicines use after the policy change. ARIMA models were used to correct for autocorrelation and stationarity. Only the SSRIs saw a significant rise in level of generic utilisation (0.2 DDD/TIM; P < 0.001) and a fall in originator usage (-0.1 DDD/TIM; P < 0.001) after the policy change. Utilisation of generic PPIs fell (level 0.06 DDD/TIM, P = 0.048; slope 0.01 DDD/TIM, P = 0.043), but utilisation of originator products also grew (level 0.05 DDD/TIM, P < 0.001; slope 0.003, P = 0.001). Generic calcium antagonists and ACE-I showed an increase in slope (0.01 DDD/TIM, P = 0.016; 0.02 DDD/TIM, P < 0.001), while the originators showed a decrease in slope (-0.003 DDD/TIM, P = 0.046; -0.01 DDD/TIM, P < 0.001). There were insufficient data on generic statin use before the policy change to allow for analysis. The mandatory offer of generic substitution appeared to have had a quantifiable effect on utilisation patterns in the 2 years after May 2003. Managed care interventions that were already in place before the intervention may have blunted the extent of the changes seen in this period. Generic policies are an important enabling provision for cost-containment efforts. However, decisions taken outside of official policy may anticipate or differ from that policy, with important consequences.

The Effectiveness of Combination Antihypertensive Therapy in Women With Hypothyroidism and the Metabolic Syndrome

Evaluating the effectiveness of the various options of combination antihypertensive therapy (AHT) in women with arterial hypertension (AH) and metabolic syndrome (MS) and hypothyroidism. The study included 163 women with hypertension, metabolic syndrome, and hypothyroidism, the median age of 53.5 (48-60) years; in 73 (44.8%) women were diagnosed with subclinical hypothyroidism (SH), 90 (55.2%) - overt hypothyroidism (OH). Patients with both SH and OH, depending on the source of the heart rate (HR) was appointed as one of the following combination of AHT. If heart rate <75 beats/min, patients (n=100) received a combination of the dihydropyridine calcium antagonist (AA) amlodipine 5 mg/day, and angiotensin receptor blockers II (ARB) losartan 50 mg/day, with heart rate >75 beats/min (n=63) - a combination of amlodipine 5 mg/day and imidazoline receptor agonist (IRA) moxonidine 200 micrograms/day. The failure to achieve target blood pressure (BP) after 4 weeks of dose drugs doubled with subsequent evaluation of the effectiveness even after 4 weeks. At baseline and after 6 months of therapy, all patients underwent daily blood pressure monitoring (DBPM). At 8 weeks, the use of a combination of AA+ARB target BP level was registered in 26 (59%) of 44 women with SH and 34 (60.7%) of the 56 - OH. In the group of women who took the AA+IRA, after 8 weeks of the target blood pressure was observed in 24 (82.8%) of 29 patients with SH and 28 (82.4%) of 34 - to OH. Register the target blood pressure was observed significantly more frequently (p<0,05) when using a combination of AA+IRA compared with AA+ARBs as with SH and OH. As a result of the combination of DBPM AA and ARBs in patients with SH and OG provided a significant reduction in average daily, daytime and nighttime systolic and diastolic blood pressure (SBP and DBP), the time index of SBP and DBP during the day and night hours. The therapy of AA and IRA regardless of the severity of hypothyroidism, there was a significant improvement in all indicators DBPM: average daily, daytime and nighttime SBP and DBP, time index and variability in SBP and DBP during the day and at night. Furthermore, as in the SH and OH significantly more pronounced positive changes most DBPM parameters were recorded using IRA in combination with AA compared with a combination AA+ARB. Significant increase in the number of women with optimal BP daily profile "dipper" observed only when using amlodipine and moxonidine. In women with hypertension, hypothyroidism and MS, regardless of the severity of decline of thyroid function and combination of the dihydropyridine AA IRA had an advantage over the AA combination with ARBs, since most patients provided achieving target blood pressure and clinically significant positive impact on BPM indicators. The results can be used in selecting the optimal AHT in patients with hypertension, MS, and the manifest subclinical hypothyroidism.

Calcium antagonists in pharmacotherapy in patients with concomitant cardiac pathology: priorities of the recommendations in clinical practice

The article discusses the problem of using calcium antagonists in clinical practice. Physicians' judgments in prescribing calcium antagonists showed its compliance with current guidelines for the treatment of hypertension. Emphasizes the feasibility of dihydropyridine calcium antagonists as efficacy and safety tools in patients with combination of arterial hypertension, stable angina and chronic heart failure. The article discusses the results of clinical efficacy studies of felodipine in a combined cardiac pathology with cognitive impairment.

Clinical efficacy of combined use of physical training and a fixed combination of an angiotensin receptor blocker II - valsartanumand the calcium antagonist - amlodipine on ambulatory (III) stage of rehabilitation in smoking patients with comorbid diseases (coronary heart disease, hypertension and chronic obstructive pulmonary disease)

Goal. The study of the clinical efficacy of combined use of systematic physical training (PT) and a fixed combination of a blocker of receptors for angiotensin II (ARB), valsartanum (Val) to dihydropyridine calcium antagonist (AA) with amlodipine (AML), appointed as part of standard therapy for smokers in patients with cardio-pulmonary pathology outpatient (III) stage of rehabilitation. Material. The study included 30 men aged 40 to 65 years. All patients were treated with statins, aspirin, .-blockers, selective and systematic FT performed 3 times a week for 4 months (duration of the training - 60 minutes with a period of moderate intensity training load of 50-60% of the threshold power cycling). After randomization, patients were divided into two groups: Group 1 (n=12) received additional angiotensin converting enzyme inhibitors (ACEI) and 2nd (n=18) - the combined preparation Exforge ® (AML 5-10 mg/Val 60 mg). Study duration - 4 months. Methods. In a study conducted clinical examination, bicycle stress test (VEM-test), echocardiography (echocardiography), ambulatory blood pressure monitoring (ABPM), spirometry, determination of concentrations of lipids and lipoproteins, glucose, fibrinogen, uric acid, creatinine, a calculation of glomerular filtration rate by MDRD. They used questionnaires: Hospital Anxiety and Depression Scale (HADS), St George's Hospital (SGRQ) and quality of life (QOL) SF-36. Results. Against the background of the FT, combined with taking an ACE inhibitor or a fixed combination of AML/Val, reduced the number of smoked cigarettes at 20.8±5.2 pieces (

T-Type Calcium Channel: A Privileged Gate for Calcium Entry and Control of Adrenal Steroidogenesis.

Intracellular calcium plays a crucial role in modulating a variety of functions such as muscle contraction, hormone secretion, gene expression, or cell growth. Calcium signaling has been however shown to be more complex than initially thought. Indeed, it is confined within cell microdomains, and different calcium channels are associated with different functions, as shown by various channelopathies. Sporadic mutations on voltage-operated L-type calcium channels in adrenal glomerulosa cells have been shown recently to be the second most prevalent genetic abnormalities present in human aldosterone-producing adenoma. The observed modification of the threshold of activation of the mutated channels not only provides an explanation for this gain of function but also reminds us on the importance of maintaining adequate electrophysiological characteristics to make channels able to exert specific cellular functions. Indeed, the contribution to steroid production of the various calcium channels expressed in adrenocortical cells is not equal, and the reason has been investigated for a long time. Given the very negative resting potential of these cells, and the small membrane depolarization induced by their physiological agonists, low threshold T-type calcium channels are particularly well suited for responding under these conditions and conveying calcium into the cell, at the right place for controlling steroidogenesis. In contrast, high threshold L-type channels are normally activated by much stronger cell depolarizations. The fact that dihydropyridine calcium antagonists, specific for L-type channels, are poorly efficient for reducing aldosterone secretion either in vivo or in vitro, strongly supports the view that these two types of channels differently affect steroid biosynthesis. Whether a similar analysis is transposable to fasciculata cells and cortisol secretion is one of the questions addressed in the present review. No similar mutations on L-type or T-type channels have been described yet to affect cortisol secretion or to be linked to the development of Cushing syndrome, but several evidences suggest that the function of T channels is also crucial in fasciculata cells. Putative molecular mechanisms and cellular structural organization making T channels a privileged entry for the “steroidogenic calcium” are also discussed.

Development of fast dissolving oral films containing lercanidipine HCl nanoparticles in semicrystalline polymeric matrix for enhanced dissolution and ex vivo permeation

Lercanidipine is a vasoselective dihydropyridine calcium antagonist, mainly used for the treatment of hypertension and angina pectoris. However, it suffers from food dependent absorption, poor solubility, low permeability and considerable first pass metabolism, resulting in highly variable and low bioavailability of 10%. Nanoparticles of lercanidipine were incorporated in fast dissolving oral films (FDO) via preparation of nanosuspension by evaporative antisolvent precipitation method. Prepared nanosuspensions were incorporated in FDO without lyophilizing or spray drying. Two nanosuspensions containing PEG 400 and TPGS 1000 as stabilizers, were selected further for incorporation in FDO. Physicochemical and mechanical properties of the optimized films were observed to be within acceptance criteria. SEM images as well as FTIR chemical images of oral films show uniform distribution of nanoparticles in polymeric matrix. The DSC and XRD results proved the poorly crystalline nature of lercanidipine. However thermal processing of film induces crystallinity in hypromellose which results in embedding of amorphous drug nanoparticles in semicrystalline polymeric matrix. Superior dissolution and permeability properties of nanoparticles were confirmed by in vitro dissolution studies and about 4.5-folds higher ex vivo drug permeation was observed from formulation through porcine buccal mucosa. This may give the clue for enhancement of bioavailability in vivo via improving orotransmucosal absorption.

Urinary catecholamines and the relationship with blood pressure and pharmacological therapy.

Our aim was to assess the importance of the sympathetic nervous system as assessed by urinary catecholamine measurement in the aetiology of essential hypertension and the importance of antihypertensive therapy in the excretion of urinary catecholamines. Twenty-four-hour urinary catecholamine measurement was performed in 1925 patients who were referred for treatment of hypertension and grouped according to the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification: of the 655 untreated patients, 59 were normotensive individuals (SBP < 140 and DBP < 90 mmHg), n = 219 stage 1 (SBP 140-159 or DBP 90-99 mmHg), n = 236 stage 2 (SBP 160-179 or DBP 100-109 mmHg) and n = 141 stage 3 (SBP ≥ 180 or DBP ≥ 110 mmHg). There was a statistically significant positive relationship between 24-h urinary norepinephrine excretion and the severity of hypertension, such that the higher the blood pressure the higher the urinary norepinephrine excretion (mean ± standard error of mean): normotensive group, 221 ± 13 nmol/24 h; stage 1, 254 ± 8 nmol/24 h; stage 2, 263 ± 7 nmol/24 h and stage 3, 296 ± 12 nmol/24 h (P < 0.001). The above relationship remained highly significant when corrected for urinary creatinine, weight, age and sex. No differences were found with urinary epinephrine or dopamine excretion. Urinary norepinephrine excretion was increased in those patients taking single-drug therapy with either a long-acting dihydropyridine calcium antagonist or a β-blocker. Our results demonstrate that in untreated hypertensive patients, urinary norepinephrine excretion is increased in proportion to the severity of blood pressure rise and also in patients taking a long-acting dihydropyridine calcium antagonist or a β-blocker. Sympathetic overactivity may play a role in the aetiology and maintenance of essential hypertension.

COMPARISON OF EFFECTIVENESS OF COMBINATION ANTIHYPERTENSION THERAPY IN WOMEN WITH ABDOMINAL OR GLUTEO-FEMORAL OBESITY

Aim. To study the influence of combinational antihypertension therapy including inhibitor of angiotensin converting enzyme (ACEi) or direct renin inhibitor (DRI) on the parameters of 24-hour blood pressure monitoring (ABPM) in postmenopausal women in different obesity patterns. Material and methods. Totally, 168 women studied with arterial hypertension (AH) in postmenopause: 97 with abdominal obesity (AO) and 71 with gluteofemoral (GFO). Patients were randomized to groups of ACEi therapy and diuretic or DRI and diuretic. Follow-up lasted for 24 weeks. Results. In 4 weeks of therapy with the usage of maximal ACEi dosages, target level of blood pressure (BP) was reached in 30 from 42 (71,4%) women with AO and 27 from 32 (84,4%) with GFO, and maximum dose of DRI led to target pressure achievement in 37 from 41 (90,2%) women with AO and 30 from 33 (90,9%) with GFO. Others required addition to the therapy a dihydropyridine calcium antagonist. In 6 months of therapy in all groups of patients there was positive dynamics of the main 24-hour profile parameters. Conclusion . Combination of ACEi or DRI with indapamide retard have significant antihypertension effect in women with AH in AO and GFO. In addition, combination of DRI with diuretic is better than of ACEi that was showed by the prevalence and speed of target BP achievement, more significant dynamics of ABPM parameters and positive changes in patients spread upon physiologic and pathologic types of 24-hour profile in 24-week therapy, especially in AO.

Антагонисты кальция в фармакотерапии у пациентов с сочетанной кардиальной патологией: приоритеты рекомендаций в реальной клинической практике

The article discusses the problem of using calcium antagonists in clinical practice. Physicians' judgments in prescribing calcium antagonists showed its compliance with current guidelines for the treatment of hypertension. Emphasizes the feasibility of dihydropyridine calcium antagonists as efficacy and safety tools in patients with combination of arterial hypertension, stable angina and chronic heart failure. The article discusses the results of clinical efficacy studies of felodipine in a combined cardiac pathology with cognitive impairment.

Effectiveness of combined antihypertensive treatment depending on the phenomenon of salt sensitivity in patients with refractory arterial hypertension

Purpose of study - evaluate the effectiveness of combined antihypertensive treatmentthat includes direct renin inhibitor in salt-sensitive and salt-resistant patients with refractory hypertension (RHT).Methods and materials. The study included 192 patients with RHT. Based on the results of the V.I.Kharchenko test and a variation of combined antihypertensive therapy, all patients were randomized into groups: group 1 - salt-sensitive patients treated with an ACE inhibitor (ACEI), dihydropyridine calcium antagonist (CA), thiazide diuretic (TD) and direct renin inhibitor aliskiren (subgroup 1A) or b-blocker - BB (subgroup 1B); group 2 - salt-resistant patients treated with ACE inhibitors, dihydropyridine CA, TD and aliskiren (subgroup 2A) or BB (subgroup 2B). In the absence of achieving target BP after 6 weeks from the start of observation, patients started receiving five-component treatment: ACE inhibitor, CA, TD, BB and aliskiren. Initially and after 48 weeks of observation, all patients underwent ambulatory blood pressure monitoring (ABPM).Results. In the group of salt-sensitive patients treatment including aliskiren contributed to achievement of target values of BP in 43.3%, and with pre- scription of BB - in 54.3% of patients. In both groups there was a significant improvement in most of the parameters of ABPM, more pronounced when using BB. Normalization of circadian BP profile was registered significantly more often ( p

Treatment of hypertension in patients with ischemic heart disease

The article deals with the burning question of treatment of hypertension in patients with ischemic heart disease. Hypertension is one of the major modifiable risk factors for stroke, heart failure, and ischemic heart disease. Arterial hypertension and ischemic heart disease are often comorbid conditions with common pathogenetic mechanisms. Because of the huge social significance of these diseases and their complications it is extremely important to find ways to improve efficacy of treatment of patients with these concomitant conditions. According to the clinical pharmacology data and the results of numerous clinical studies, dihydropyridine calcium antagonists turned out to be an effective treatment for hypertension in combination with ischemic heart disease. Through the example of calcium channel blockers, amlodipine in particular, the efficacy of this group of drugs for treating patients with hypertension and high risk for cardiovascular complications was demonstrated. Amlodipine exhibits antihypertensive, anti-anginal and antiatherosclerotic properties and is able to protect myocard. Moreover, amlodipine has a favourable safety profile, which preconditions its extensive use in clinical practice, in particular for the treatment of hypertension in combination with ischemic heart disease.

Development of a reservoir type prolonged release system with felodipine via simplex methodology.

Background and aimsFelodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method.MethodsThe first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models.ResultsA 12 hours release was achieved using granules with the size between 315–500 μm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method.ConclusionWe have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models.