RESUMEN

Introducción: Los estudios de solubilidad y la obtención de datos fisicoquímicos de fármacos en disolventes puros pertenecientes a diferentes clases químicas resultan claves para desarrollar nuevas formulaciones de medicamentos. En este trabajo se calcularon los parámetros de solubilidad parciales de Hansen (HSP) para evaluar la miscibilidad y las interacciones intermoleculares del barnidipino en diecisiete disolventes puros. Además, se compararon los valores experimentales obtenidos con los teóricos calculados según la estructura del barnidipino, para analizar la influencia de las relaciones soluto-soluto, soluto-solvente de los grupos de contribución aditivos, en las propiedades químicas y físicas del barnidipino con los solventes de diferente polaridad ensayados, para aportar información relevante para su uso en la industria farmacéutica. Método: La solubilidad en equilibrio del barnidipino en los disolventes seleccionados se determinó usando el método clásico de agitación en matraces seguida de un análisis por espectrofotometría UV a 298,15 K, y se calcularon los parámetros parciales de solubilidad con la aplicación de métodos teóricos de contribución de grupo, propuestos por Hoftyzer-Van Krevelen y Fedors. El modelo KAT-LSER se usó para investigar el efecto del solvente basado en el concepto de relaciones de energía de solvatación lineal. La fracción molar se obtuvo considerando las densidades de las soluciones. Los análisis en fase sólida se realizaron por calorimetría diferencial de barrido. Resultados: La modificación introducida en el método de Hansen, es decir, el empleo de lnX2 como variable dependiente proporcionó excelentes resultados. Los valores más altos de solubilidad se han encontrado en los disolventes polares. Se observa que las interacciones intermoleculares solvente-solvente y soluto-solvente con enlaces de hidrógeno y fuerzas de van der Waals, influyeron significativamente en la solubilidad del fármaco. (AU)

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Introduction: Solubility studies and obtaining physicochemical data on drugs in pure solvents belonging to differ-ent chemical classes are key to developing new drug formulations. In this work, Hansen partial solubility parame-ters (HSP) were calculated to assess the miscibility and intermolecular interactions of barnidipine in seventeen pure solvents. The comparison of the results obtained with the theoretical values calculated according to the structure of barnidipine, were valuable to analyse the influence of the solute-solute, solute-solvent relationships of the additive contribution groups, on the chemical and physical properties of this molecule with the solvents of different polarity tested, to provide relevant information highly useful in the pharmaceutical industry. Method: Equilibrium barnidipine solubilities in mono-solvents was determined using the classical shake-flask method, followed by UV-spectrophotometric analysis at 298.15 K. The partial solubility parameters were calculated by applying theoretical group contribution methods, proposed by Hoftyzer-Van Krevelen and Fedors. The KAT-LSER model was used to investigate the effect of solvent based on the concept of linear solvation energy relationships. The mole fraction was obtained from the densities of the solutions. Solid-phase analyses were made by calorimetry differential scanning. Results: The modification introduced in the extended Hansen method, that is, the use of lnX2 as the dependent variable, provided excellent results. The highest solubility values have been found in polar solvents. It is observed that solvent-solvent and solute-solvent intermolecular interactions through hydrogen bonds and van der Waals forces, significantly influence drug solubility (AU)

Asunto(s)

Humanos , Nifedipino , Composición de Medicamentos , Solubilidad , Preparaciones Farmacéuticas/química , Solventes

RESUMEN

An experimental combination of analytical quality by design and green analytical chemistry approaches is introduced to develop an high-performance thin-layer chromatography (HPTLC) approach to quantify barnidipine hydrochloride in the pharmaceutical matrix. The analytical quality by design approach was introduced to green analytical chemistry to enhance protocol knowledge while ensuring efficiency and reducing environmental impacts, energy consumption and analyst visibility. This analytical approach was systematically addressed by exploring failure mode effect analysis, risk assessment and optimization design. Subsequently, a screening of primary variables was performed to select the aptest proportion of solvents in the mobile phase resulting from the principles of green analytical chemistry. Failure mode effect analysis and a risk assessment study were attempted to estimate the critical method parameters (CMPs). The influence of the CMPs on critical analytical attributes, i.e. retention factor and peak area, was assessed through a screening design. A response surface methodology was then executed for the critical analytical attributes as a concern of the determined CMPs, and the conditions for excellent resolution were determined using a desirability procedure. The established protocol was validated in compliance with the International Conference on Harmonization guideline Q2(R1) and showed excellent specificity and sensitivity.

Asunto(s)

Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Tecnología Química Verde/métodos , Nifedipino/análogos & derivados , Límite de Detección , Modelos Lineales , Nifedipino/análisis , Reproducibilidad de los Resultados , Proyectos de Investigación

RESUMEN

OBJECTIVE: Increased intracellular calcium concentration plays an important role in the secondary mechanism of spinal cord injury. In the presenting experimental study, we aimed to evaluate the healing effect of barnidipine, which has a high affinity for L-type calcium channels, on acute spinal cord injury and to compare its effects with those of methylprednisolone. METHODS: A total of 32 Spraque Dawley albino adult female rats were divided into 4 groups; group 1: sham-operated (n=8), group 2: only ischemia (n=6), group 3: barnidipine-treated (n=8), and group 4: methylprednisolone-treated (n=6). An ischemia-reperfusion model was created by clipping the abdominal aorta in the rats. Motor examination was performed 1 hour after the surgical procedure and before sacrification. Immediately following the second motor examination, rats were sacrificed and tissue samples were taken for histopathological examination and for testing of tissue malondialdehyde (MDA) levels. RESULTS: A significant correlation of motor examination was found between the sham-operated and barnidipine-treated groups and the sham-operated and only ischemia groups at the 1st and 24th hour (p<0.008). There was no significant difference between the only ischemia and barnidipine-treated groups and only ischemia and methylprednisolone-treated groups (p>0.008). Light microscopic examination of the sham-operated group revealed findings consistent with normal spinal cord structure. In group 2, 3, and 4, light microscopic examination revealed polymorphonuclear leukocyte infiltration and a small amount of axonal swelling. There was no significant correlation between the ischemia and barnidipine-treated groups and the barnidipine and methylprednisolone groups in terms of MDA levels (p>0.008). CONCLUSION: A single dose of barnidipine (10 mg/kg) and methylprednisolone are not effective and not sufficient to prevent spinal ischemia-reperfusion injury in rats.

RESUMEN

Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guidelines support a substantial equivalence amongst various antihypertensive drug classes. However, several studies have also reported clinically relevant differences among antihypertensive drugs, in terms of both BP lowering efficacy and tolerability/safety profile. These differences should be taken into account not only when adopting first-line antihypertensive therapy, but also when titrating or modulating combination therapies, with the aim of achieving effective and sustained BP control. This review will briefly describe evidence supporting the use of dihydropyridinic calcium channel blockers for the clinical management of hypertension, with a particular focus on barnidipine. Indeed, this drug has been demonstrated to be effective, safe and well tolerated in lowering BP levels and in reducing hypertension-related organ damage, thus showing a potential key role for improving the clinical management of hypertension.

Asunto(s)

Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , Hipertensión Esencial/tratamiento farmacológico , Cumplimiento de la Medicación , Nifedipino/análogos & derivados , Vasodilatadores/uso terapéutico , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Dihidropiridinas/efectos adversos , Hipertensión Esencial/diagnóstico , Hipertensión Esencial/fisiopatología , Humanos , Nifedipino/efectos adversos , Nifedipino/uso terapéutico , Factores de Riesgo , Resultado del Tratamiento , Vasodilatadores/efectos adversos

RESUMEN

INTRODUCTION: Hypertension is the leading cause of cardiovascular disease worldwide. Calcium channel blockers are an effective antihypertensive treatment, but frequently hypertension remains uncontrolled for many patients, partly due to tolerability issues. AIM: To assess the tolerability and effectiveness of barnidipine in mild to moderate hypertension patients switching treatment from other calcium channel blockers in daily practice. METHODS: BASIC-HT, a prospective real life study, enrolled 20,479 hypertensive patients initiating barnidipine treatment. The present paper focuses on a subgroup of patients in BASIC-HT for whom the previous treatment with amlodipine or lercanidipine was replaced by barnidipine. Tolerability and effectiveness of barnidipine in these patients were assessed at two visits during a 3-month follow up. RESULTS: In 1710 mild to moderate hypertension patients switching treatment from amlodipine or lercanidipine to barnidipine monotherapy or in combination with other antihypertensive drug classes, mean blood pressure decreased during 3-month follow-up. The mean systolic blood pressure decreased from 153.15 mmHg [95% CI 152.35-153.95] at baseline to 139.20 mmHg [95% CI 138.58-139.82] at visit 3, after 3 months. The mean diastolic blood pressure decreased from 88.85 mmHg at baseline [95% CI 88.36-89.34], to 81.56 mmHg [95% CI 81.20-81.91] at visit 3. Among these patients, 65.4% replaced their initial calcium channel blocker treatment to barnidipine for tolerability reasons. During the follow-up, the main adverse event reported was edema (4.8%). The nature and frequency of events reported in this subgroup of switcher patients were in line with those reported by the total population in BASIC-HT. CONCLUSION: This real-life study suggests that replacement of other calcium channel blockers with barnidipine is a valuable therapeutic option, especially when tolerability is an issue.

Asunto(s)

Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Dihidropiridinas/administración & dosificación , Sustitución de Medicamentos , Hipertensión/tratamiento farmacológico , Nifedipino/análogos & derivados , Anciano , Amlodipino/efectos adversos , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/efectos adversos , Dihidropiridinas/efectos adversos , Sustitución de Medicamentos/efectos adversos , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Nifedipino/administración & dosificación , Nifedipino/efectos adversos , Vigilancia de Productos Comercializados , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of barnidipine, a strong lipophilic calcium channel blocker, in younger (≤55 for efficacy or <65 years for adverse events) versus older (>55 or ≥65 years) patients with uncomplicated hypertension. METHODS: 20,275 patients received barnidipine, 10 or 20 mg/day, as monotherapy or in combination with other antihypertensive drug(s) in the observational BArnidipine real-life Safety and tolerability In Chronic HyperTension (BASIC-HT) study. Efficacy and tolerability were assessed over a 3-month period. The present paper describes results from prespecified subgroup analyses by age not reported elsewhere. RESULTS: Both age groups showed a clinically meaningful decrease in blood pressure (BP) over time (p<0.0001). The mean systolic and diastolic BP after approximately 3 months of barnidipine therapy was well below the target value of <140/90 mmHg for individual patients, with no notable differences between age groups. The decrease in mean pulse pressure was greater in patients >55 years (-10.8 mmHg) than in patients ≤55 years (-8.7 mmHg) (p<0.0001) and the proportion of patients with pulse pressure >60 mmHg decreased from 61.1% at baseline to 24.8% at Visit 3 in patients >55 years and from 47.7% to 16.5% in patients ≤55 years (p<0.0001).The overall incidence of adverse events was low, leading to treatment discontinuation in only 3.0-3.6% of patients. Peripheral edema, a common adverse effect with calcium channel blockers in clinical practice, was reported by 2.7% of patients aged <65 years and by 4.6% of patients aged ≥65 years. CONCLUSION: The efficacy and tolerability profiles of barnidipine as monotherapy or in combination with other antihypertensive drugs were shown to be favorable in both younger and older patients in a real-life practice setting. Randomized double-blind controlled studies are needed to confirm these results.

RESUMEN

BACKGROUND: Essential hypertension has been extensively reported to cause endothelial dysfunction. The aim of this study was to evaluate the effects of barnidipine or lercanidipine, in addition to losartan, on some parameters indicative of endothelial damage and oxidative stress in hypertensive, type 2 diabetic patients. METHODS: One hundred and fifty one patients were randomised to barnidipine, 20 mg/day, or lercanidipine, 20 mg/day, both in addition to losartan, 100 mg/day, for 6 months. We assessed BP every month, in addition, patients underwent ambulatory blood pressure monitoring (ABPM). We also assessed: fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), some markers such as high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), metalloproteinase-2 (MMP-2) and -9 (MMP-9), soluble vascular adhesion protein-1 (sVCAM-1), soluble intercellular adhesion protein-1 (sICAM-1), isoprostanes and paraoxonase-1 (PON-1). RESULTS: Both barnidipine and lercanidipine resulted in a significant reduction in blood pressure, even if the reduction obtained with barnidipine + losartan was greater than that obtained with lercanidipine + losartan. Data recorded with ABPM also showed a similar trend. Barnidipine + losartan reduced the levels of Hs-CRP, TNF-α, sVCAM-1, sICAM-1, and isoprostanes both compared to baseline and to lercanidipine + losartan. CONCLUSIONS: Barnidipine + losartan gave an improvement of some parameters indicative of endothelial damage and oxidative stress in diabetic and hypertensive patients. TRIAL REGISTRATION: NCT02064218 , ClinicalTrials.gov.

Asunto(s)

Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dihidropiridinas/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Losartán/uso terapéutico , Nifedipino/análogos & derivados , Estrés Oxidativo/efectos de los fármacos , Anciano , Antihipertensivos/efectos adversos , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Dihidropiridinas/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/fisiopatología , Italia , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , Nifedipino/efectos adversos , Nifedipino/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

UNLABELLED: The aim of this study was to evaluate the effects of perindopril or barnidipine alone or combined with simvastatin on metabolic parameters and hepatic steatosis degree. One hundred and forty nine mild to moderate hypertensive, normocholesterolemic, overweight or obese outpatients with hepatic steatosis were enrolled. They were treated with perindopril 5mg/day, or barnidipine, 20mg/day, for 6 months; subsequently simvastatin, 20mg/day was added to both treatments for further 6 months. Blood pressure variation was recorded. Patients also underwent an ultrasound examination, at baseline and after 6, and 12 months. We also assessed: fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), tumor necrosis factor-α (ΤΝF-α), interleukin-6 (IL-6), high-sensitivity C reactive protein (Hs-CRP). Both perindopril and barnidipine reduced blood pressure, with barnidipine being more effective. Barnidipine, but not perindopril, slightly decreased total cholesterol and triglycerides after 6 months compared to baseline; lipid profile improved in both groups when simvastatin was added. Regarding inflammatory parameters, barnidipine reduced TNF-a, IL-6, and Hs-CRP, both in monotherapy, and after simvastatin addition. Hepatic steatosis parameters improved only when simvastatin was added. We can conclude that barnidipine better reduced blood pressure compared to perindopril and inflammatory parameters. Regarding hepatic steatosis parameters, only the addition of simvastatin improved them. REGISTRATION NUMBER: NCT02064218, ClinicalTrials.gov.

Asunto(s)

Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Nifedipino/análogos & derivados , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Perindopril/uso terapéutico , Simvastatina/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Nifedipino/uso terapéutico , Obesidad/tratamiento farmacológico

RESUMEN

The present study was aimed to investigate the influence of Barnidipine treatment on early stage hypertension by determining the function and morphology of the mesenteric and renal arteries as well as the kidney in N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME)-induced hypertensive rats. Barnidipine (3 mg/kg/day p.o) was applied to rats after 2 weeks of L-NAME (60 mg/kg/day) administration, and continued for the next 3 weeks concomitantly with L-NAME. The systolic blood pressure (SBP) of rats was determined to decrease significantly in Barnidipine treated hypertensive group when compared to that of rats received L-NAME alone. Myograph studies demonstrated that the contractile reactivity to noradrenaline were significantly reduced in both of the resistance arteries while endothelium-dependent relaxations to acethylcholine were significantly diminished particularly in the mesenteric arteries of L-NAME-induced hypertensive rats. The impaired contractile and endothelial responses were completely restored by concomitant treatment of Barnidipine with L-NAME. Histopathological examinations verified structural alterations in the arteries as well as the kidney. Moreover, a decrease in endothelial nitric oxide synthase (eNOS) expression was presented both in the arteries and kidney of hypertensive rats which were increased following Barnidipine treatment. Elevated plasma levels of malondialdehyde (MDA) and myeloperoxidase (MPO) were also reduced in Barnidipine treated hypertensive rats. In conclusion, besides to its efficacy in reducing the elevated SBP, amelioration of vascular function, modulation of arterial and renal eNOS expressions as well as reduction of the plasma levels of oxidative and inflammatory biomarkers are possible supportive mechanisms mediating the favorable implications of Barnidipine in L-NAME-induced hypertension model.

Asunto(s)

Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Hipertensión/tratamiento farmacológico , Enfermedades Renales/prevención & control , Riñón/efectos de los fármacos , Arterias Mesentéricas/efectos de los fármacos , NG-Nitroarginina Metil Éster , Nifedipino/análogos & derivados , Arteria Renal/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/patología , Hipertensión/fisiopatología , Mediadores de Inflamación/metabolismo , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Masculino , Malondialdehído/metabolismo , Arterias Mesentéricas/metabolismo , Arterias Mesentéricas/patología , Arterias Mesentéricas/fisiopatología , Nifedipino/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Ratas Wistar , Arteria Renal/metabolismo , Arteria Renal/patología , Arteria Renal/fisiopatología , Factores de Tiempo , Remodelación Vascular/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos

RESUMEN

INTRODUCTION: Blood pressure (BP) is generally poorly controlled in hypertensive patients. One cause is poor adherence to drugs, which can be improved by treatments combining good efficacy and tolerability. Barnidipine is a strong lipophilic calcium channel blocker (CCB) with efficacy similar to other dihydropyridines. OBJECTIVE: BASIC HT is an observational study in a large population of patients with essential hypertension to evaluate the tolerability of barnidipine in a real-life setting. METHODS: 20479 patients were enrolled in the study. Tolerability and efficacy was assessed at 2 visits during a 3-month period. 20275 patients were included in the analysis. RESULTS: Adverse events were reported by 10.6% of the patients, leading to treatment discontinuation in 3%. Events were those expected with CCBs. The drop-out rate was 8%. Mean systolic and diastolic pressure decreased from 159.6 to 138.2 and from 92.5 to 81.7 mmHg. CONCLUSION: The decrease in BP, is probably due to stimulation of good adherence by barnidipine.

Asunto(s)

Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Nifedipino/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Bloqueadores de los Canales de Calcio/efectos adversos , Femenino , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Nifedipino/efectos adversos , Nifedipino/uso terapéutico , Adulto Joven

RESUMEN

BACKGROUND: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure. OBJECTIVE: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine. METHODS: This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140-179 mm Hg and diastolic BP of 90-109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets. RESULTS: Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, -10.3/-9.4 vs -16.6/-9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13%]; P < 0.05). CONCLUSION: In this small sample of treatment-naive hypertensive patients, the antihypertensive effect of barnidipine 10 mg once daily was not significantly different from that of amlodipine 5 to 10 mg once daily.

RESUMEN

BACKGROUND: Barnidipine is one of a new generation of dihydropyridine calcium-channel blockers. Despite evidence of favorable effects on blood pressure (BP) and insulin sensitivity, this drug has rarely been tested in hypertensive patients with metabolic syndrome (MS). OBJECTIVE: The aim of this study was to evaluate the effects of barnidipine on BP and left ventricular (LV) diastolic function in patients with hypertension and MS. METHODS: Consecutive subjects aged 18 to 75 years with systolic BP (SBP) of 140 to 179 mm Hg and/or diastolic BP (DBP) of 90 to 109 mm Hg and MS (based on Adult Treatment Panel III criteria) were assessed for inclusion in the study. Lifestyle changes according to current guidelines were recommended and barnidipine monotherapy 10 mg daily was initiated. All patients entered a 2-week run-in period. After a 6-week treatment period, the daily dosage was doubled for the remainder of the study in patients whose BP remained uncontrolled (≥140/≥90 mm Hg). We assessed the glycolipidic profile and LV structure and function using standard Doppler and tissue Doppler imaging (TDI) echocardiography before and after 12 weeks of treatment. Ambulatory BP records and electrocardiographic and echocardiographic tracings were coded and shipped to a central laboratory for blinded analysis. Possible adverse events (AEs) were recorded at predetermined intervals throughout the follow-up period and at unplanned intervals whenever an AE became known to the investigators. RESULTS: Thirty-four consecutive patients were assessed for inclusion. Thirty consecutive patients (20 men, 10 women; mean {SD| age, 55.9 {10.3| years; 5 current smokers) were included in the study. At study entry, mean office SBP was 146 mm Hg, DBP was 87 mm Hg, and heart rate was 72 beats/min. At the study end, mean office SBP/DBP was <140/90 mm Hg in 20 patients (66.7%). From baseline to study end, 24-hour ambulatory BP decreased significantly by 12 and 8 mm Hg for SBP and DBP, respectively (both, P = 0.001). The smoothness index was 0.92 for SBP and 0.82 for DBP. Fasting plasma glucose concentration decreased significantly from 110 to 104 mg/dL (P = 0.001). Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. From baseline to study end, there were no significant changes in LV structure or systolic function (LV mass, 50.7 vs 50.6 g/ht(2.7); LV diastolic/systolic diameters, 47.50/29.80 vs 48.40/30.76 mm; wall motion score index, 1.0 vs 1.0; ejection fraction, 61% vs 60%), while the peak E/A velocity ratio on TDI increased from 1.078 to 1.245 (P = 0.009). No AEs (including AEs reflected by chemistry values) either unrelated or related to treatment were noted during the 12-week duration of the study. CONCLUSIONS: In these hypertensive patients with MS, a 12-week treatment period with barnidipine in addition to lifestyle modifications was associated with significant reductions in 24-hour BP and BP variability, reduction in plasma glucose concentration, and improvement in LV diastolic relaxation. No significant changes in lipid concentrations, LV structure, or systolic function were found.

RESUMEN

BACKGROUND: The goal of antihypertensive therapy will be to extended the life expectancy of hypertensive patients to that of subjects without high blood pressure. Hypertension treatment in the 1990s will focus on the mechanisms by which blood pressure is lowered by various antihypertensive agents, as will as individualization of drug therapy. In recognition of their lack of adverse lipid effects and their tolerability, first line therapy with alpha blocker, angiotensin converting enzyme inhibitors and calcium antagonists will become increasingly commom. We studied a new dihydropyridine calcium antagonist barnidipine to evaluate the efficacy and safety in patients with essential hypertension. METHODS: The rabit aortic rings were cut and mounted on the force transducer to record an isometric tension on polygraph. To elucidate the mechanism of saponin effect on vascular smooth muscle, the contractility of the vascular smooth muscle were measured under vatying experimental condition. RESULTS: 1) The baseline sitting systolic and diastolic blood pressure after 4 weeks washout period were 154.+/-15.9mmHg and 1.0+/-8.2mmHg. At the end of 8 weeks of therapy sitting systolic and diastolic blood pressure were 126+/-9.5mmHg and 84.5+/-4.6mmHg which declined statistically significant(p<0.05). 2) The pulse rates did not change significantly during treatment period(70.0+/-6.6 beats / min at baseline, 70.9+/-7.2 beats / min at 2 weeks, 71.2+/-5.0 beats / min at 4 weeks, 72.8+/-8.5 beats / min at 6 weeks, and 71.9+/-6.8 beats / min). 3) The adverse reactions due to branidipine were reported in 2 patients(6.5%) with headache, 2 patients(6.5%) with facial flushing, 1 patient(3.4%) with dizziness and 1 patients(3.4%) with nausea and vomiting). 4) The abnormal laboratory findings due to barnidipine were reported in 1 patient with increased total bilirubin and GPT, 1 patient with increased transaminase and 1 patient with CK but another findings were normal. CONCLUSION: These results indicate that barnidipine is effective and safe antihypertensive agent in the treatment of essential hypertension.

Asunto(s)

Humanos , Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Bilirrubina , Presión Sanguínea , Calcio , Mareo , Quimioterapia , Rubor , Cefalea , Frecuencia Cardíaca , Hipertensión , Esperanza de Vida , Músculo Liso Vascular , Náusea , Saponinas , Transductores

RESUMEN

Objective To compare and assess the antihypertentive efficacy and safety of barnidipine hydrochloride and felodipine in the elderly hypertentive patients. Methods 69 elderly patients(60-75 years old ) with mild or moderate essential hypertension were selected and randomly assigned to two groups, one was medicated with barnidipine (36 patients) and another (33 patients) with felodipine. Placeboes were given for 2 weeks, then the testees were administered barnidipine 10mg/d or felodipine 5mg/d for 2 weeks, followed by an increased administration of dose titration to barnidipine 15mg/d or felodipine 10mg/d for another 2 weeks in those patients with DBP≥90mmHg. Both groups were administered once daily. Results After 4 weeks administration no statistical difference was found on the total effectiveness between barnidipine and felodipine groups (100.0% vs 93.9%). Both SBP and DBP declined by 20.7?7.8mmHg and 17.6?4.5mmHg respectively in barnidipine group, and 20.2?9.6mmHg and 17.6?6.1mmHg respectively in felodipine group. The decline of blood pressure showed no significant difference between the two groups. The mild harmful respond occurred in 4 of 36 patients of barnidipine group (11.1%), and in 3 of 33 patients of felodipine group(9.1%).Conclusion The results suggested that barnidipine is effective and well tolerated in antihypertension of the old patients.