Drug Amlodipine Research Articles

Inhibition of Ostwald ripening in heptane/water miniemulsions

The Ostwald ripening has been shown to cause the degradation of model low-concentrated heptane/water miniemulsions containing, as the only stabilizer, Tween 80 (Tw), hydroxypropyl cellulose (HPC), a drug (amlodipine (Am) or felodipine (F)), or a promoter of skin permeability (glyceryl monooleate (GMO)). The efficiency of the Ostwald ripening inhibition increases in the following series: Am < Tw < GMO < HPC < F. The analysis of different mechanisms of the Ostwald ripening inhibition by the hydrophilic (Tw, HPC) and lipophilic (Am, F, GMO) surface-active stabilizers has resulted in the preparation of a stable high-concentrated miniemulsion containing F, GMO, HPC, and Tw, this emulsion being promising for pharmaceutical fields of application.

FORMULATION AND EVALUATION OF BILAYER TABLETS OF TWO INCOMPATIBLE DRUGS AMLODIPINE BESILATE AND LOSARTAN POTASSIUM

The main goal of this study was to develop a stable formulation fo r two incompatible anti hypertensive drugs Amlodipine besilate and Losartan potassium as an immediate release bi layer tablet and to evaluate its dissolution studies. The formulation development work was initiated with wet granulation for losartan potassiu m layer and direct compression for amlodipine besilate layer. Super disintegrants like Crospovidone, Sodium starch glycolate (SSG) were used in all the formulations and its role on disintegration and dissolution properties of the drug were studied. The pre pared tablets were evaluated for weight variation, wetting time, hardness, thickness, friability, % drug content, disintegration time, in vitro drug release. Formulation F8 showed a highest drug release of 84.02 % for amlodipine besilate and 90.08 % for lo sartan potassium in 30 minutes which was selected as optimized formulation and considered for further studies. The stability studies, shown that the formulation F8 was stable enough at 40 ◦ C / 75 % RH for a period of 6 months. The results suggest the feasib ility of developing bi layer tablets consisting of amlodipine besilate and losartan potassium for the convenience of patients with hypertension.

A FIXED COMBINATION OF PERINDOPRIL AND AMLODIPINE IN HYPERTENSIVE PATIENTS WITH ACUTE CORONARY SYNDROME: A CLINICAL EXPERIENCE

Objective. To assess the eficacy and tolerability of a ixed combination of perindopril and amlodipine in patients with acute coronary syndrome and hypertension III stage 2 and 3 degree.Results and conclusion. The drug (perindopril plus amlodipine 10/5 mg) was shown to provide a high 24-hour antihypertensive eficacy, leading to a signiicant decrease in blood pressure and heart rate. The drug was well tolerated, and the drug withdrawal was not required.

Liquid chromatographic method for the simultaneous determination of captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulation, and human serum by programming the detector

A highly sensitive LC method with UV detection has been developed for the simultaneous determination of coadministered drugs captopril, piroxicam, and amlodipine in bulk drug, pharmaceutical formulations, and human serum at the isosbestic point (235 nm) and at individual λmax (220, 255, and 238 nm, respectively) by programming the detector with time to match the individual analyte's chromophore, which enhanced the sensitivity with linear range. The assay involved an isocratic elution of analytes on a Bondapak C18 (10 μm, 25 × 0.46 cm) column at ambient temperature using a mobile phase of methanol/water 80:20 at pH 2.9 and a flow rate of 1.0 mL/min. Linearity was found to be 0.25-25, 0.10-6.0, and 0.20-13.0 μg/mL with correlation coefficient >0.998 and detection limits of 7.39, 3.90, and 9.38 ng/mL, respectively, whereas calibration curves for wavelength-programmed analysis were 0.10-6.0, 0.04-2.56, and 0.10-10.0 μg/mL with correlation coefficient >0.998 and detection limits of 5.79, 2.68, and 3.87 ng/mL, respectively. All the validated parameters were in the acceptable range. The recovery of drugs was 99.32-100.39 and 98.65-101.96% in pharmaceutical formulation and human serum, respectively, at the isosbestic point and at individual λmax . This method is applicable for the analysis of drugs in bulk drug, tablets, serum, and in clinical samples without interference of excipients or endogenous serum components.

A Validated Stability-Indicating RP-LC Method for the Simultaneous Determination of Amlodipine and Perindopril in Tablet Dosage Form and Their Stress Degradation Behavior Under ICH-Recommended Stress Conditions

A stability-indicating RP-LC assay method was developed for the simultaneous determination of the cardiovascular drugs amlodipine and perindopril in the presence of degradation products generated from forced decomposition studies. The developed method is applicable for the determination of related substances in bulk drugs and simultaneous assay in a tablet pharmaceutical dosage form. Separation of the drugs and their degradation products was obtained using an RP Waters Spherisorb ODS1 column (250 x 4.6 mm id, 5 pm particle size) with the mobile phase acetonitrile-water (30 + 70, v/v) containing 15 mM phosphoric acid. The pH of the mobile phase was adjusted to 5.0. A flow rate of 1.2 mL/min was used for the separations, with detection at 215 nm. The chromatographic separation was performed at a column temperature of 45 degrees C. Atenolol was chosen as the internal standard. Amlodipine and perindopril were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Degradation studies showed that both compounds were degraded under these stress conditions. The method was found to be stability-indicating and can be used for the routine analysis of amlodipine and perindopril in the studied combined tablet dosage form.

Вплив амлодипіну та бісопрололу на ультраструктуру міокарда щурів зі спонтанною артеріальною гіпертензією

Calcium channel blockers and beta1-adrenoblockers are effective antihypertensive agents, but their cell protective properties are not investigated well. Spontaneously hypertensive rats received a 10 mg/kg/day amlodipine dose and 25 mg/kg/day bisoprolol dose via an orogastric tube during three months. We performed examination of the myocardium's fragments under a scanning electron microscope. Morphometric investigation of mitochondrions we performed using special program what is named "ORGANELLE". Amlodipine significantly normalizes the ultrastructure of the myocardium. This antihypertensive drug prevented the signs of over-contractility of myofibrils. Amlodipine causes the fusion mitochondrions which has compensatory character on the background of good safety of mitochondrial ultrastructures. Another feature of amlodipine is a significant increase in the number of capillaries. Bisoprolol significantly reduced over-contractility of the myofibrils, but the signs of dystrophic-destructive processes in myofibrils and mitochondrions of cardiomyocytes remained. Bisoprolol improved the condition of the endothelial cells, but the activation of the functional activity of these cells has not been observed. The combined use of two antihypertensive drugs amlodipine and bisoprolol led to a better recovery of myofibrils than their separate use, whereas the effect on mitochondrions noted similar as in the group of rats received bisoprolol and that effect was worse than during amlodipine's monotherapy. Also we didn't reveal a reason to combine these drugs after analysis of the effect of the drug combination on the conditions of blood microvessels, which number was increased compared with hypertensive rats, but significantly less than when rats received only amlodipine. These essential cell-protective effects of amlodipine and bisoprolol in spontaneously hypertensive rats could be a significant additional factor in the treatment of hypertension complicated with pathological changes in the heart.

Mononuclear transition and non-transition complexes of amlodipine besylate as antihypertensive agent: synthesis, spectral, thermal, and antimicrobial studies

Mononuclear Mn(II), Co(II), Ni(II), Zn(II), Cd(II), Mg(II), Sr(II), Ba(II), Ca(II), Pt(IV), Au(III), and Pd(II) complexes of the drug amlodipine besylate (HL) have been synthesized and characterized by elemental analysis, spectroscopic technique (IR, UV–Vis, solid reflectance, scanning electron microscopy, X-ray powder diffraction, and 1H-NMR) and magnetic measurements. The elemental analyses of the complexes are confirmed by the stoichiometry of the types [M(HL)(X)2(H2O)]·nH2O [M = Mn(II), Co(II), Zn(II), Ni(II), Mg(II), Sr(II), Ba(II), and Ca(II); X = Cl− or NO3 −], [Cd(HL)(H2O)]Cl2, [Pd(HL)2]Cl2, [Pt(L)2]Cl2, and [Au(L)2]Cl, respectively. Infrared data revealed that the amlodipine besylate drug ligand chelated as monobasic tridentate through NH2, oxygen (ether), and OH of besylate groups in Mn(II), Co(II), Ni(II), Zn(II), Cd(II), Mg(II), Sr(II), Ba(II), Ca(II), and Au(III) complexes, but in Pt(IV) and Pd(II) complexes, the amlodipine besylate coordinates via NH2 and OH (besylate) groups. An octahedral geometry is proposed for all complexes except for the Cd(II), Pt(IV), and Pd(II) complexes. The amlodipine besylate free ligand and the transition and non-transition complexes showed antibacterial activity towards some Gram-positive and Gram-negative bacteria and the fungi (Aspergillus flavus and Candida albicans).

Development and Validation of a Reversed-Phase Ultra-Performance Liquid Chromatographic Method for the Simultaneous Determination of Six Drugs Used for Combined Hypertension Therapy

A simple, rapid, and reliable ultra-performance LC assay method has been developed for the simultaneous estimation of orally administered hypertension drugs (atenolol, hydrochlorothiazide, amlodipine besylate, indapamide, nifedipine, and lercanidipine hydrochloride), any of which may be administered with atenolol in combined hypertension therapy. Chromatography was carried out at 25 degrees C on a 2.1 x 50 mm id, 1.7 microm particle size Acquity BEH C18 column with the isocratic mobile phase 0.01 M, 4.0 pH aqueous phosphate buffer-acetonitrile (50 + 50, v/v) at a flow rate of 0.35 mL/min. All drugs were separated in less than 4 min with good resolution and minimal tailing, without interference by excipients. The method was validated according to International Conference on Harmonization guidelines, and the acceptance criteria for accuracy, precision, linearity, specificity, and system suitability were met in all cases. The column effluent was monitored at 230 nm. The detector response was linear in the range of 1-20 microg/mL of these drugs. LOD obtained was 0.04 microg/mL for atenolol, 0.02 microg/mL for hydrochlorothiazide, 0.03 microg/mL for amlodipine besylate, 0.03 microg/mL for indapamide, 0.02 microg.mL for nifedipine, and 0.01 microg/mL for lercanidipine hydrochloride. The suggested method has the advantage that all the drugs can be quantified alone or in combination with atenolol using a single mobile phase.

Joint solubilization of lipophilic drug amlodipine and glyceryl monolaurate in aqueous micellar solutions of Tween 80

The solubilization of lipophilic amlodipine (Am is a antihypertensive drug) and nonionic surfactant glyceryl monolaurate (GML is a skin permeation enhancer), as well as their joint solubilization (co-solubilization) have been measured by UV spectroscopy and refractometry in aqueous micellar solutions of Tween 80 (Tw). The properties of mixed micelles (Tw + GML, Tw + Am, Tw + GML + Am) have been studied, including the aggregation number of components, the localization of solubilizates, diffusion coefficients, the size and the degree of hydration. As a result of co-solubilization, (Tw + GML + Am) three-component micelles contain 4.2 times more molecules of the drug than (Tw + Am) two-component micelles. The experimental data on the kinetics of mass transfer of Am by micelles based on Tw are in good agreement with the calculations under diffusion theory; furthermore, three-component micelles carry Am more effectively than two-component micelles.

Semisolid matrix-filled hard gelatin capsules for rapid dissolution of amlodipine besilate: Development and assessment

The objective of the study was to prepare semisolid capsules (SSCs) of poorly water-soluble drug amlodipine besilate (AB) using a combination of technologies involving solid dispersion (SD) preparation and converting it into semisolid matrix filled in hard gelatin capsules (termed as SSCs) with the aim of reducing lag time in drug release and to improve the dissolution rate. AB is used for its anti-arrhythmic, anti-anginal, and anti-hypertensive activity. These are the emergency activities which should be treated as fast as possible like in the case of angina attack (heart attack). Any lag time that is generated due to its poor dissolution can add on in this emergency and that can be avoided by developing a readily dissolvable formulation: SDs of AB. SD of AB was prepared by fusion method using varying combinations of Poloxamer 407 and Plasdone S630. A total of nine batches (SD1–SD9) were characterized for the in vitro dissolution behavior in phosphate buffer pH7.4. SD8 with 95.8% cumulative drug release in 60 min, t50% = 4.1 min and DE30 Min = 84.2% were selected for the development of the semisolid matrix. Differential scanning calorimetry of SD8 revealed molecular dispersion of AB and Plasdone S630 in Poloxamer 407. SD8 was then formulated as SSCs using gelucire 44/14 and PEG 400 as semisolid components and PEG 6000 as a suspending agent to achieve the reduction in lag time for drug release. A total of seven SSC formulations were prepared and evaluated for drug release. Formulation of SSC4 showed maximum cumulative drug release (CDR) of 98.9% within 20 min that was almost a threefold reduction in the time required to achieve similar CDR by SD of AB. Thus, SSCs present an excellent approach to enhance the dissolution as well as to reduce the lag time of dissolution for poor water-soluble drugs especially to those therapeutic classes that are intended for faster onset of action.

The Biochemical and Histopathological Investigation of Amlodipine in Ethylene Glycol-Induced Urolithiasis Rat Model

Background: Urinary calculi are a common and severe problem, which are formed by urolithiasis or by the formation of calcium oxalate (CaOx) crystals in the kidneys. Many treatment options such as drugs, various herbal preparations, surgical removal of the stones, and extracorporeal shock wave lithotripsy have been applied for this condition. The aim of this study is to assess the effects of the drug amlodipine in an experimentally induced urolithiasis rat model. Materials and methods: The effect of 5 mg/kg amlodipine was studied in rats that were first treated with 1% ethylene glycol and 1% ammonium chloride for 21 days to induce urolithiasis. The weight differences and the levels of calcium, magnesium, and phosphate were measured in serum and urine. In addition, urine CaOx level was defined and histopathological analyses were performed on the kidneys. Results: Urolithiasis caused a significant increase in both serum and urine parameters compared with healthy rats. Urolithiasis plus amlodipine administration increased the levels of these same parameters. Urine CaOx level was high in urolithiasis rats and was also increased by urolithiasis plus amlodipine administration. The weight of the rats decreased in the urolithiasis plus amlodipine group when compared with the urolithiasis group. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in the urolithiasis group and the amlodipine treatment group. Conclusion: We showed that amlodipine may increase susceptibility to urolithiasis by raising hyperoxaluria and hypercalciuria. Further studies should be performed to elucidate the urolithiasis activity of amlodipine and to confirm the data.

English

ObjectiveTo investigate the myocardial depressant activity of a newly synthesised dihydropyrimidine derivative 5-acyl-6-methyl-4-phenyl-2 -S-ethyl-1,4-dihydropyrimidine (BK vi) and comparing with nifedipine on Isolated perfused rabbit heart. Material and MethodsEffects of the test compound BK-vi on the amplitude,heart rate and coronary flow on isolated perfused rabbit heart was compared with nifedipine.Observations were made with increasing concentrations of BK-vi and Nifedipine with dimethylsulfoxide (DMSO) as the solvent.Six preparations were used for each dose of BK-vi and nifedipine.Heart rate ,amplitude and coronary flow were noted down every minute for five minutes after injection of each drug and control. ResultsOn comparing the effects of BK-vi and nifedipine, it was found that both had a negative inotropic and negative chronotropic effect. Compound BK -vi did not produce significant effect on heart rate at all the four doses. In comparison, nifedipine produced a significant to highly significant decrease in heart rate.Significant decrease in amplitude with BK-vi was seen at dose of 7.29 X 10-4M and 14.5 X 10-4M by 42% and 56.98% respectively and in coronary flow by 39.95% at dose of 14.5 X 10-4M .Nifedipine significantly decreased heart rate and amplitude at all doses with cardiac arrest at 4.6 X 10-5M.A significant increase in coronary flow was seen with nifedipine by 9.4% and 13% at doses of 0.5 X 10-5M and 1.15 X 10-5M respectively though this property was lost at higher doses.On comparison, BK-vi produced significant myocardial depression at much higher dose than nifedipine. ConclusionBK-vi has calcium channel blocking activity like nifedipine and produced less potent myocardial depression in comparison with nifedipine. Key wordsDihydropyrimidines, Voltage dependent calcium channels, Nifedipine, Dihydropyridines International Journal of Medical and Clinical Research ISSN:0976-5530 & E-ISSN:0976-5549, Volume 3, Issue 3, 2012 Introduction Modern drug discovery involves screening small molecules for their ability to bind to a preselected protein target as well as to modulate a biological pathway in cells [1].The demand for diverse compound libraries for screening in drug discovery is the driving force behind the development of new technologies for rapid parallel and combinatorial synthesis [2].Bignelli in 1893 first described the synthesis of 6-methyl-4-substituted phenyl 2-oxo-1,2,3,4tetrahydropyrimidine-5-carboxylic acid ethyl esters by condensation of an aldehyde, urea and ethyl acetoacetate [3] .DHP (Dihydropyridines) and DHPMs(Dihydropyrimidines) represent important and extensively studied compounds belonging to the class of calcium channel blockers.Many researchers have determined the synthetic routes and biological activities of these compounds.These developments led to the pharmacological evaluation of these compounds [4]. Much interest has been shown in the design of Bignelli-like compounds which are valuable substitutes for the nifedipine and other 1,4-dihydropyridine drugs [5], regarded as aza-analogues of nifedipine related dihydropyridines [6].Out of the diverse range of biological activities shown by dihydropyrimidines, most notable is the cardiovascular activity that compares favourably with activity shown by structurally related drugs amlodipine, nicardipine. A reasonable pharmacophore model for DHP/DHPM calcium channel modulators has been proposed Citation: Shalini Salwan, et al (2012) Myocardial Depressant Activity of a Newly Synthesised Dihydropyrimidine Derivative 5-acyl-6-methyl4-phenyl-2-S-ethyl-1, 4-dihydropyrimidine (bk-vi) in comparison with nifedipine. International Journal of Medical and Clinical Research, ISSN:0976-5530 & E-ISSN:0976-5549, Volume 3, Issue 3, pp.-132-135. Copyright: Copyright©2012 Shalini Salwan, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Synthesis of 1,4-dihydropyridine using microwave-assisted aza-Diels–Alder reaction and its application to Amlodipine

We synthesized 1,4-dihydropyridine skeleton using aza-Diels–Alder reaction under the microwave irradiation condition which has become a powerful method for the rapid synthesis of a variety of organic molecules. The prepared 1,4-dihydropyridine product was further converted to antihypertensive drug Amlodipine to test this new methodology.

Investigation of the effects of the chronic administration of some antihypertensive drugs on enzymatic and non-enzymatic oxidant/antioxidant parameters in rat ovarian tissue

Objective. In this study, effects of chronic antihypertensive drug (clonidine, methyldopa, amlodipine, ramipril, and rilmenidine) treatment on antioxidant–oxidant parameters were investigated in rat ovarian tissue.Study design. Chronic drug administration for 30 days and at the end, biochemical examinations (total glutathione (tGSH), glutathione peroxidase (GPO), glutathione reductase (GR), glutathione s-transferase (GST), superoxide dismutase (SOD), nitric oxide (NO), catalase (CAT), malondialdehyde (MDA), and myeloperoxidase (MPO) analyses) were performed.Results. The levels of glutathione (GSH) and NO, and the activities of GPO, GR, GST, SOD, and CAT were measured the lowest in ramiprile group. Also in ramiprile group, the level of MDA and the activity of MPO was the highest.Conclusion. We divided the drugs into four groups according to their biochemical side effect potentials in ovarian tissue: (I) Drugs which have no clear negative effect on ovarian tissue: clonidine, rilmenidine; (II) Drugs which have mild negative effect on ovarian tissue: methyldopa; (III) Drugs which have moderate negative effect on ovarian tissue: amlodipine; (IV) Drugs which have severe negative effect on ovarian tissue: ramipril. These data might be useful in the selection of the least toxic antihypertensive drug in pregnant and/or normal females.

Stability Indicating LC Method For the Simultaneous Determination of Amlodipine and Olmesartan in Dosage Form

A simple, rapid, and precise method is developed for the quantitative simultaneous estimation of amlodipine (AM) and olmesartan (OL) in combined pharmaceutical dosage form. A chromatographic separation of the two drugs was achieved with an ACE 5 C(18) 25-cm analytical column using buffer-acetonitrile (60:40, v/v). The resolution between OL and AM was found to be more than 12. Theoretical plates for OL and AM were 6970 and 11,841, respectively. Tailing factor for OL and AM was 0.90 and 0.98, respectively. OL, AM, and combination drug product were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Peak homogeneity data of OL and AM is obtained by photodiode array detector in the stressed sample chromatograms, demonstrating the specificity of the method for their estimation in presence of degradation product. The described method shows excellent linearity over a range of 20-400 microg/mL for OL and 5-100 microg/mL for AM. The correlation coefficient for OL and AM are 0.9995 and 0.9998, respectively. The relative standard deviation for six measurements in two sets of each drug in tablets is always less than 2%. The proposed method was found to be suitable and accurate for quantitative determination and stability study of OL and AM in pharmaceutical preparations.

L-type calcium channel blockers and Parkinson disease in Denmark.

This study was undertaken to investigate L-type calcium channel blockers of the dihydropyridine class for association with Parkinson disease (PD), because some of these drugs traverse the blood-brain barrier, are potentially neuroprotective, and have previously been evaluated for impact on PD risk. We identified 1,931 patients with a first-time diagnosis for PD between 2001 and 2006 as reported in the Danish national hospital/outpatient database and density matched them by birth year and sex to 9,651 controls from the population register. The index date for cases and their corresponding controls was advanced to the date of first recorded prescription for anti-Parkinson drugs, if prior to first PD diagnosis in the hospital records. Prescriptions were determined from the national pharmacy database. In our primary analyses, we excluded all calcium channel blocker prescriptions 2 years before index date/PD diagnosis. Employing logistic regression analysis adjusting for age, sex, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity score, we found that subjects prescribed dihydropyridines (excludes amlodipine) between 1995 and 2 years prior to the index date were less likely to develop PD (odds ratio, 0.73; 95% confidence interval, 0.54-0.97); this 27% risk reduction did not differ with length or intensity of use. Risk estimates were close to null for the peripherally acting drug amlodipine and for other antihypertensive medications. Our data suggest a potential neuroprotective role for centrally acting L-type calcium channel blockers of the dihydropyridine class in PD that should be further investigated in studies that can distinguish between types of L-type channel blockers.

Lack of effect of short-term treatment with Amlodipine and Lisinopril on retinal autoregulation in normotensive patients with type 1 diabetes and mild diabetic retinopathy

Diabetic retinopathy is characterized by morphological changes in the retina secondary to disturbances in retinal blood flow. It has been shown that antihypertensive treatment has a protective effect on the development of diabetic retinopathy, and evidence suggests that inhibitors of the renin-angiotensin system have a protective effect beyond the antihypertensive effect. The background for this additional effect is unknown but might be related to an effect on retinal autoregulation. In a double-blinded, two-way cross-over study, 25 normotensive patients with type 1 diabetes (T1D) aged 20.6-33.9 (mean 27.9) with mild retinopathy were randomized to receive either 5 mg of the calcium channel blocker (CCB) amlodipine for 14 days followed by a washout period and treatment with 10 mg of the angiotensin converting enzyme (ACE) inhibitor lisinopril for another 14 days or the two treatments in the reverse order. Using a Dynamic Vessel Analyzer (DVA), the diameter response of retinal arterioles during an acute increase in the blood pressure induced by isometric exercise, during flicker stimulation and during both stimulus conditions simultaneously was studied before and during the two treatments periods. Amlodipine and lisinopril induced a similar non-significant decrease in the arterial blood pressure. At baseline, the arterial diameter decreased by 2.4 ± 0.9% (p = 0.004) during isometric exercise, increased by 2.2 ± 0.9% (p = 0.019) during flicker stimulation and increased by 1.8 ± 0.9% (p = 0.03) during the combined stimulus conditions. Neither of the antihypertensive drugs amlodipine (p = 0.76) or lisinopril (p = 0.11) changed the diameter response of retinal vessels significantly; however, the two treatments induced a different response in the veins during combined exercise and flicker (p = 0.021). Short-term treatment with amlodipine and lisinopril had no significant effect on retinal autoregulation in young normotensive patients with T1D and mild retinopathy, and this lack of effect was similar for the two drugs. A possible normalizing effect of antihypertensive treatment on retinal autoregulation was not observed; however, it might take longer time to improve autoregulation than to reduce the arterial blood pressure.

Differential roles of dihydropyridine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin-induced renal tubular toxicity in rats

In the present study, we investigated the antioxidative potencies of dihydropyridine calcium antagonists prototype nifedipine, the second generation drug nitrendipine, and the long acting, third generation drug amlodipine on gentamicin-induced renal tubular toxicity in Sprague–Dawley rats. In addition, we analyzed the relationship between renal tubular cell apoptosis and the antioxidative properties of these dihydropyridine calcium antagonists. Results showed that treatment with gentamicin alone caused significant changes in the levels of urinary protein, urinary N-acetyl-beta- d-glucosaminidase, serum creatinine, and blood urea nitrogen. Nifedipine and amlodipine effectively reversed the effect of gentamicin on these parameters. In contrast, nitrendipine either had no effect or worsened gentamicin-induced changes in the levels of urinary protein, urinary N-acetyl-beta- d-glucosaminidase, serum creatinine, and blood urea nitrogen. Furthermore, gentamicin treatment caused significant increases in the levels of malondialdehyde, nitric oxide, nitric oxide synthase and significant decreases in the levels of reduced glutathione, glutathione-S-transferase, and superoxide dismutase in kidney tissues. These effects were dramatically reduced by nifedipine and amlodipine but not affected by nitrendipine. In addition to the biochemical changes, histopathological studies showed that gentamicin caused structural damages in the kidneys; renal tubular cell apoptosis, a decrease in Bcl-2 expression and an increase in Bax expression were observed in all rats treated with gentamicin, nifedipine and amlodipine effectively reversed the effect of gentamicin while nitrendipine worsened them. In conclusion, this study clearly indicated that nifedipine and amlodipine protected against gentamicin-induced nephrotoxicity while nitrendipine had little effect, or even worsened.

In vitro and in vivo efficacies of amlodipine against Listeria monocytogenes

Listeria monocytogenes causes suppurative gastritis in BALB/c mice. We investigated the effect of the antihypertensive drug amlodipine (Aml) on the growth of L. monocytogenes in vitro and in vivo. Aml showed noteworthy inhibitory action (minimum inhibitory concentration, MIC(90) 32 microg/ml) against Listeria strains and demonstrated cidal (minimum bactericidal concentration, MBC 64 microg/ml) activity. Aml administered orally at 2.5 microg/g in female BALB/c mice for 7 days, commencing 4 days before oral challenge (1 x 10(8) CFU/ml with L. monocytogenes ATCC 51774), significantly reduced bacterial counts in the stomach (P < 0.01), liver (P < 0.01), and spleen (P < 0.05), and decreased (P < 0.05) gastric lesions, neutrophilic infiltration, edema, vascular degeneration, and necrosis of gastric tissues. It caused the down-regulation of expression of inflammatory cytokines (IFN-gamma, IL-1 beta, and TNF-alpha) compared to drug-free control. Aml may be used in the presence of an antibiotic as adjunct therapy that boosts the host immunity against Listeria. Further, QSAR studies might contribute in manipulating it as a lead compound for the synthesis of new, more effective non-antibiotics (helper compounds), perhaps devoid of side-effects, that could be recommended as compassionate therapy for listeriosis.

Use of adsorptive square-wave anodic stripping voltammetry at carbon paste electrode for the determination of amlodipine besylate in pharmaceutical preparations

The antihypertensive drug amlodipine has been characterized voltammetrically in a carbon paste electrode by means of anodic stripping voltammetry. An adsorptive stripping method in a carbon paste electrode for trace determination of amlodipine has been described. Cyclic voltammetric studies indicated the oxidation of amlodipine besylate at the electrode surface through a single two-electron irreversible step fundamentally controlled by adsorption. A study of the variation in the peak current with solution variables such as pH, ionic strength, concentration of amlodipine, possible interference, and instrumental variables, such as preconcentration time and accumulation potential, has resulted in the optimization of the oxidation signal for analytical purposes. By anodic adsorptive anodic stripping voltammetry, the calibration plot was linear in the range 9.9 × 10−9 − 1.4 × 10−7 M with a detection limit of 2 × 10−10 M in a carbon paste electrode at pH 11.0. The procedure was successfully applied to the assay of amlodipine besylate in some commercial products in the market (Amlopres®, Amlodipine, and Norvasc®). The percentage recoveries were in agreement with those obtained by the reference method.