Amlodipine

The subanalysis of a 4 Â 4 factorial, 8-week study to evaluate the efficacy and tolerability of telmisartan (T) 40-80 mg/ amlodipine (A) 5-10 mg used in treatment-naïve patients (n ¼ 231) and patients previously treated with antihypertensive agents (n ¼ 880). Similar blood pressure (BP) reductions were achieved with T þ A, regardless of their pretreatment status. Highest reductions were achieved with T80 þ A10 (treatment-naïve À26.5/À18.2 mm Hg and previously treated À25.6/ À19.9 mm Hg). Most patients (treatment-naïve 72.4% and previously treated 77.6%), including those with added risk, achieved BP goal (<140/90 mm Hg) with T80 þ A10. Tolerability was comparable in both groups.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, doubleblind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 ¼ 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 ¼ 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). Intrial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P ¼ .005, race-by-amlodipine/lisinopril interaction P ¼ .012) and gender (gender-by-lisinopril/amlodipine interaction P ¼ .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period. J Am Soc Hypertens 2014;8(11):808-819.

Background: Hypertension (HTN) or high blood pressure is a chronic medical condition in which the blood pressure in the arteries is elevated. Hypertension is a cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. This has resulted in significant morbidity and mortality. Hypertension related complications manifest as target-organ damage which include cardiovascular disease and are the primary causes of the death in hypertensive patients. Organ systems adversely affected by the hypertension include heart, brain, kidneys, peripheral arterial disease and eyes. Objectives: The objectives of this work is to study the drug prescription pattern in patients with hypertension and with related comorbidities (DM,STROKE,CKD,CVD) and to study the outcome of therapy in terms of reduction in blood pressure and also to educate the patients about disease and lifestyle adaptations. Materials and Methods: It was a Prospective observational stud...

What is known and objective: Drug-induced thrombocytopenia (DITP) may be a fatal adverse reaction to many drugs. It is often misdiagnosed as primary immune thrombocytopenia (ITP), and thus diagnosis can be delayed and patients can be treated inappropriately. Amlodipine a calcium-channel blocker, and simvastatin, a statin, have very rarely been implicated in DITP. We report on an investigation of the causal relationship of amlodipine and simvastatin with thrombocytopenia occurring in the same patient, and review the literature. Case summary: We present the case of a 78-year-old female hypertensive diabetic patient with three successive DITPs. The first attack of acute severe thrombocytopenia occurred after a 2week course of amlodipine, and was initially misdiagnosed as ITP. Her platelet count normalized after the amlodipine was discontinued. The second attack followed her restarting simvastatin 3 weeks later. She had stopped it 2 months earlier having previously taken it for over 5 years. Again, she recovered once the simvastatin was discontinued. The third DITP attack occurred when she accidently took a single dose of amlodipine 9 months later. What is new and conclusion: We provide clear evidence of a causal association of amlodipine with thrombocytopenia, and probable evidence of a causal association of simvastatin with thrombocytopenia. This is the first reported case of DITPs occurring with two of the most widely prescribed drugs in the same patient. Many hypertensive patients need to take multiple drugs in order to achieve their treatment goals and this increases their risk of drug-induced adverse reactions and makes identification of the causal drug (or drugs) extremely difficult.

The objective of the study was to demonstrate that reduction in mean 24-hour diastolic blood pressure with 160 mg valsartan and 12.5 mg hydrochlorothiazide was not inferior to 10 mg amlodipine in hypertensive blacks. A total of 482 blacks with stage 1 and stage 2 hypertension (mean seated blood pressure 140 to 180/90 to 110 mm Hg) were enrolled in a double-blind, randomized, prospective study. After a placebo run-in period, patients were randomized to 160 mg valsartan or 5 mg amlodipine for 2 weeks, then force-titrated to 160 mg valsartan and 12.5 mg hydrochlorothiazide or 10 mg amlodipine for an additional 10 weeks. Blood pressure was assessed by 24-hour ambulatory blood pressure monitoring. Other assessments included quality of life, peripheral edema, and safety. Noninferiority of valsartan/hydrochlorothiazide to amlodipine was demonstrated by comparable reductions in mean 24-hour diastolic blood pressure with both treatments (Ϫ10.2Ϯ8.6 mm Hg versus Ϫ9.1Ϯ8.3 mm Hg, respectively; PϽ0.001 for noninferiority), as well as in mean 24-hour systolic blood pressure (Ϫ15.9Ϯ12.1 mm Hg versus Ϫ14.5Ϯ12.2 mm Hg; PϽ0.001 for noninferiority). The proportion of patients reporting adverse events and the incidence of most events were similar in both treatment groups, although more patients treated with amlodipine reported peripheral edema (5.8% versus 1.7%; Pϭ0.03) and joint swelling (2.9% versus 0%; Pϭ0.008) compared with valsartan/hydrochlorothiazide. We conclude that a starting dose of valsartan/hydrochlorothiazide (160/12.5 mg) is as effective as high-dose amlodipine (10 mg) in reducing blood pressure in blacks with stage 1 and stage 2 hypertension, and valsartan/hydrochlorothiazide is better tolerated. (Hypertension. 2005;46:508-513.)

Bilateral hypertensive retinopathy and choroidopathy with bullous retinal detachment was diagnosed in a 17-year-old, female spayed Domestic Short-haired cat. The underlying cause of the systemic hypertension could not be determined. The blood pressure was lowered successfully with the oral application of the L-type calcium channel blocker amlodipine besylate. The cat subsequently regained vision. The improvement in retinal function was documented using electroretinography.

Our aim was to prove the feasibility and safety of a protocol for early and protected discharge 1 day after carotid endarterectomy (CEA) using a system of telemedicine (TMD) monitoring. Among 147 patients operated upon for 163 CEAs, we selected a group (A) of 36 patients fulfilling criteria for discharge 1 day after surgery. An electronic blood pressure manometer, a videophone, an antihypertensive drug (amlodipine), and a customer satisfaction questionnaire were given to every group A patient. With a video-communication program linked to the Web, we monitored every 4 hours (from 8:00 a.m. to 8:00 p.m.) for 2 days the surgical wound, blood pressure, and heart frequency of the patients. Other patients were included in group B. No differences regarding demographic characteristics, risk factors, carotid lesions, operative time, postoperative complications, or blood loss were noted between group A and group B. Twenty-one patients in group A were actually discharged 1 day after surgery. No cervical hematoma developed. Three hypertensive crises were treated successfully in group A. From the questionnaire a feeling of insecurity at discharge emerged, but it rapidly resolved. The overall cost of video connections was 25.39 ± 0.25 Euros per patient. CEA can be safely done as 1-day surgery using a TMD monitoring system in selected cases. Our protocol allowed early discharge safely, leading to reduced hospital costs.

In addition to reducing blood pressure, antihypertensive drugs should modify other atherosclerotic risk factors. One such risk factor is the prothrombotic state, which is characterised mainly by increased fibrinogen and plasminogen activator inhibitor-1 levels and abnormalities in platelet function. Platelet activity and aggregation potential can be estimated by measuring mean platelet volume (MPV). Serotonin plays a role in vasospasm and increased platelet aggregation capacity, and has been shown to increase MPV in vitro. However, serotonin levels and MPV have not been studied in the metabolic syndrome. We evaluated mean platelet volume (MPV) in patients with the metabolic syndrome, and compared the effects of doxazosin and amlodipine on MPV and serum serotonin level in patients with this condition. Thirty-eight patients who met the Adult Treatment Panel III criteria for the metabolic syndrome and 20 healthy controls were included in the study. Patients were randomised into two gro...

tensive treatment in elderly patients in terms of cardiovascular morbidity and mortality rate reduction. 7-11 However, because the risk of side effects is a major concern when treating the elderly, the use of low-dose combination treatments may be of particular interest.

Four, accurate, precise, and sensitive spectrophotometric methods are developed for the simultaneous determination of a ternary mixture containing amlodipine besylate (AM), olmesartan medoxomil (OL) and hydrochlorothiazide (HZ), where AM is determined at its λ(max) 364.6 nm ((0)D), while (OL) and (HZ) are determined by different methods. Method (A) depends on determining OL and HZ by measuring the second derivative of the ratio spectra ((2)DD) at 254.4 and 338.6 nm, respectively. Method (B) is first derivative of the double divisor ratio spectra (D-(1)DD) at 260.4 and 273.0 nm for OL and HZ, respectively. Method (C) based on successive spectrophotometric resolution technique (SSRT). The technique starts with the ratio subtraction method then measuring OL and HZ at their isoabsorptive point at 260.0 nm, while HZ is measured using the amplitude of first derivative at 335.2 nm. Method (D) is mean centering of the ratio spectra (MCR) at 252.0 nm and 220.0 nm for OL and HZ, respectively....

sea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial sug-gest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.

We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07±0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29±0.11 mg/kg per day for those <13 years, 0.16±0.11 mg/kg per day for those ≥13 years, 0.23±0.14 mg/kg per day for essential, hypertension and 0.24±0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.

Objectives The use of low-dose amlodipine has not yet been well established in the elderly. This study therefore aimed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension. Patients and methods Sixty-five hypertensive individuals (aged 66.3±5.3 years) received amlodipine 2.5mg per day for 12 weeks before and

Anti-cancer chemotherapeutics involve multiple molecular targets to portray its action. The role of Dihydropyridine derivatives was found in treating hypertension and other chronic ailments. But the role of this spectrum of drug, there might be some unexplored potentials and maybe as a therapeutic agent.
Here, the action of Amlodipine Besylate, a derivative of Dihydropyridine, has been revealed and its cytotoxic and chemotherapeutic action was evident from Cell Viability Assays. To extend our observations, FACS results were analyzed to show that Amlodipine Besylate is associated with cell cycle arrest and cell death. Also, Immunofluorescence and Confocal Microscopy revealed that Amlodipine Besylate treatment led to microtubular disruption and loss of cellular integrity. Thus Amlodipine Besylate might function as a chemotherapeutic agent.

Keywords: Amlodipine Besylate, MTAs, Trypan Blue, MTT, PI-FACS, Confocal microscopy

Simple and rapid assay method is primary prerequisite in quality assurance department for any pharmaceutical dosage form. When two drugs are combined in a single dosage form, it becomes difficult to estimate them simultaneously with required accuracy and precision. Here we have proposed a simple and rapid UV spectrophotometric assay method for simultaneous determination of amlodipine besylate and valsartan in both bulk drug and commercial dosage forms. Method employed was Zero absorbance method where amlodipine and valsartan were determined at 363 nm and 290 nm respectively. At 363 nm valsartan don't have absorption and at 290 nm amlodipine has zero absorption. Linearity was established at 8 µg/mL -80 µg/mL for amlodipine (y= 0.012X + 0.002 R 2 = 0.999) and 4 µg/mL -300 µg/ml for Vasartan (y= 0.002X + 0.017 R 2 = 0.999). Method was found to be accurate and precise with %RSD<2 for all the validation parameters employed. Method was found to be very sensitive with LOD 2.4 µg/mL and 3.6 µg/mL whereas LOQ was 7.5 µg/mL and 11 µg/mL for Amlodipine besylate and Valsartan respectively. As method uses methanol as a solvent to dissolve, it is cost effective for routine analysis in quality assurance department for determination of these drugs individually or simultaneously.

The appearance of multiresistant bacterial strains coupled with the globally ongoing problem of infectious diseases point to the imperative need for novel and affordable antimicrobial drugs. The antibacterial potential of cardiovascular non-antibiotics such as amlodipine (AML), dobutamine, lacidipine, nifedipine and oxyfedrine has been reported previously. Of these drugs, AML proved to have the most significant antibacterial activity against Gram-positive and Gram-negative bacteria. Time-kill curve studies indicate that this Ca 2+ channel blocker exhibits bactericidal activity against Listeria monocytogenes and Staphylococcus aureus. AML could protect against murine listeriosis and salmonellosis at doses ranging within its maximum recommended human or non-toxic ex vivo dose. AML acts as a 'helper compound' in synergistic combination with streptomycin against several Gram-positive and Gram-negative bacterial strains in vitro as well as in the murine salmonellosis model in vivo. The present review focuses on the possible use of cardiovascular non-antibiotics such as AML as auxiliary compound targets for synergistic combinations in infections and hypertension conditions, rationalised on the basis of the activities of the compounds.

A new rapid, precise and sensitive reverse phase high performance
liquid chromatographic (RP-HPLC) method has been developed and
validated  for  the  estimation  of  Perindopril  and  Amlodipine
simultaneously  in  combined  dosage  form.  The  two  components
Perindopril  and  Amlodipine  were  well  resolved  on  an  isocratic
method,  C18  column,  utilizing  a  mobile  phase  composition  of
acetonitrile:  methanol:  a  mixed  buffer  of  0.02M  Potassium
dihydrogen  phosphate  buffer  and  0.02M  Sodium  dihydrogen
Phosphate buffer with 1mL Tri ethyl amine (40:20:40), v/v, pH 5.0)
at  a  flow  rate  of  1.0  mL/min  with  UV  detection  at  226  nm.  The
retention time of Perindopril and Amlodipine were 2.9 min and 4.9
min  respectively.  The  developed  method  was  validated  for
specificity,  linearity,  precision,  accuracy,  limit  of  detection  (LOD),
limit of quantification (LOQ) and robustness as per ICH guidelines.
Linearity for Perindopril and Amlodipine were found in the range of
48-112 µg/ml and 60.0-140.0 µg/ml, respectively. The percentage
recoveries for Perindopril and Amlodipine ranged from 98.9-100.4 %
and 98.9-100.7 %, respectively. The proposed method could be used
for routine analysis of Perindopril and Amlodipine in their combined
dosage forms.

The present study describes development and validation of simple, rapid, sensitive and stability indicating highperformance liquid chromatographic assay method for simultaneous determination of Amlodipine besylate and Valsartan in bulk as well as in commercial formulation. Analytical separation was achieved with RP Waters Symmetry C18 Column [150×4.6 mm] using a combination of methanol and potassium dihydrogen phosphate buffer [0.01 M] pH 2.5, in ratio 60:40 v/v with flow rate of 1 mL min −1 . The retention times for Amlodipine and Valsartan were found to be 4.6 and 7.6 min respectively. Both the drugs were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions individually as well as in combination, subsequently samples were analyzed by the proposed method. Detection was done by PDA detector at 238 nm. Method was found to be very sensitive as LOD found to be 20 ng/mL and 44 ng/mL for Amlodipine besylate and Valsartan respectively. The method was found to be specific and stability indicating as no interfering peaks of degradation compounds and excipients were noticed. The developed method was validated with respect to linearity, accuracy, precision, specificity, robustness as per International Conference on Harmonization (ICH) guidelines. The proposed method hence useful for the application in quality control laboratories for quantitative analysis of both the drug individually or in combination, as it is simple and rapid method with excellent accuracy and precision.

The synergistic protective effect of Nicorandil (KATP channel opener) and Amlodipine (calcium channel blocker) on heart tissue antioxidant defense system and lipid profile were examined on isoproterenol induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg−1 daily, i.p.) for 2 days showed significant changes in antioxidant defense system and lipid profile levels. Pretreatment with Nicorandil (2.5 mg kg−1 daily, p.o.) and Amlodipine (5.0 mg kg−1 daily, p.o.) for 3 days significantly prevented these alterations and restored the enzyme activities to near normal. These findings indicate the synergistic protective effect of Nicorandil and Amlodipine on tissue defense system and lipid metabolism during isoproterenol induced cardiac damage.

Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are co-formulated in a single-dose combination for the treatment of hypertension. The combination is used by patients whose blood pressure is not adequately controlled on either component monotherapy. This work describes a simple, sensitive, and reliable spectrofluorimetric method for the simultaneous determination of the two antihypertensive drugs; amlodipine besylate (AML) and valsartan (VAL) in their combined tablets. The method involved measurement of the native fluorescence at 455 nm (λ Ex 360 nm) and 378 nm (λ Ex 245 nm) for AML and VAL, respectively. Analytical performance of the proposed spectrofluorimetric procedure was statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection, and quantification limits. Regression analysis showed good correlation between fluorescence intensity and concentration over the concentration ranges 0.2-3.6 and 0.008-0.080 µg mL −1 for AML and VAL, respectively. The limits of detection were 0.025 and 0.0012 µg mL −1 for AML and VAL, respectively. The proposed method was successfully applied for the assay of the two drugs in their combined pharmaceutical tablets with recoveries not less than 98.85%. No interference was observed from common pharmaceutical additives. The results were favourably compared with those obtained by a reference spectrophotometric method.

Objectives: Amlodipine is a calcium channel blocker (CCB) known to stimulate nitric oxide production from endothelial cells. Whether this ancillary property can be related to the capacity of amlodipine to concentrate and alter the structure of cholesterol-containing membrane bilayers is a matter of investigation. Here, we reasoned that since the endothelial nitric oxide synthase is, in part, expressed in cholesterol-rich plasmalemmal microdomains (e.g., caveolae and rafts), amlodipine could interfere with this specific locale of the enzyme and thereby modulate NO production in endothelial cells. Methods and results: Using a method combining lubrol-based extraction and subcellular fractionation on sucrose gradient, we found that amlodipine, but not verapamil or nifedipine, induced the segregation of endothelial NO synthase (eNOS) from caveolin-enriched low-density membranes (8 T 2% vs. 42 T 3% in untreated condition; P < 0.01). We then performed co-immunoprecipitation experiments and found that amlodipine dose-dependently disrupted the caveolin/eNOS interaction contrary to other calcium channel blockers, and potentiated the stimulation of NO production by agonists such as bradykinin and vascular endothelial growth factor (VEGF) (+ 138 T 28% and + 183 T 27% over values obtained with the agonist alone, respectively; P < 0.01). Interestingly, we also documented that the dissociation of the caveolin/ eNOS heterocomplex induced by amlodipine was not mediated by the traditional calcium-dependent calmodulin binding to eNOS and that recombinant caveolin expression could compete with the stimulatory effects of amlodipine on eNOS activity. Finally, we showed that the amlodipine-triggered, caveolin-dependent mechanism of eNOS activation was independent of other pleiotropic effects of the CCB such as superoxide anion scavenging and angiotensin-converting enzyme (ACE) inhibition. Conclusions: This study unravels the modulatory effects of amlodipine on caveolar integrity and the capacity of caveolin to maintain eNOS in its vicinity in the absence of any detectable changes in intracellular calcium levels. The resulting increase in caveolin-free eNOS potentiates the NO production in response to agonists including VEGF and bradykinin. More generally, this work opens new avenues of treatment for drugs able to structurally alter signaling pathways concentrated in caveolae.

Hypertension is a major modifiable risk for the development of cardiovascular, cerebrovascular and renal diseases. Thus, effective treatment of high blood pressure is an important strategy for reducing disease burden; however, in spite of the availability of numerous effective therapies only 30-40 % of patients with hypertension achieve the recommended blood pressure goals of &lt;140/90 mmHg. Lack of adherence to therapy and reluctance to intensify therapy are cited frequently to explain the discrepancy between potential and attained outcomes. Adherence is closely related to the tolerability, effectiveness and complexity of therapy. Therapeutic inertia may be influenced by concerns over tolerability, as well as the lack of clear preferences for therapies when managing patients with risk factors and comorbidities. Effective and well-tolerated single pill combination therapies are now available that improve adherence and simplify treatment. The combination of a renin-angiotensin syste...

A simple, accurate and precise spectroscopic method was developed for simultaneous estimation of Amlodipine besylate and Simvastatin in synthetic mixture using Absorbance correction method. At 360.80 nm (λmax of Amlodipine besylate) Simvastatin has zero absorbance so Amlodipine besylate is directly estimate at 360.80 nm. At 237.60 nm (λmax of Simvastatin) both drugs have some absorbance so Simvastatin is estimate at 237.60 nm using absorbance correction method. The method was found to be linear (r2>0.999) in the range of 5-10 μg/ml for Amlodipine besylate at 360.80 nm. The linear correlation was obtained (r2>0.999) in the range of 5-10 μg/ml for Simvastatin at 237.60 nm. The limit of determination was 0.17 μg/ml and 0.10μg/ml for Amlodipine besylate and Simvastatin, respectively. The limit of quantification was 0. 54μg/ml and 0. 32μg/ml for Amlodipine besylate and Simvastatin, respectively. The accuracy of these method were evaluated by recovery studies and good recovery result were obtained greater than 99%. The method was successfully applied for simultaneous determination of Amlodipine besylate and Simvastatin in binary mixture.

Malignant hypertension is a well-defined condition associated with high blood pressure and acute target-organ damage. Although 95% of cases are secondary to essential hypertension, its etiological profile is broad. Juxtaglomerular cell tumor is a rare condition, with only approximately 65 cases reported to date. We describe a patient with malignant hypertension with acute renal failure and intestinal ischemia secondary to a juxtaglomerular cell tumor. We believe this is the first case of juxtaglomerular cell tumor causing malignant hypertension. The diagnostic approach and treatment are discussed. Am J Kidney Dis 46:957-961.

Background: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensinconverting enzyme inhibitor may act synergistically to reduce blood pressure (BP).

Evidence of emerging Plasmodium falciparum resistance to artemisinin-based combination therapies, documented in western Cambodia, underscores the continuing need to identify new antimalarial combinations. Given recent reports of the resurgence of chloroquine-sensitive P. falciparum parasites in Malawi, after the enforced and prolonged withdrawal of this drug, and indications of a possible synergistic interaction with the macrolide azithromycin, we sought to further characterize chloroquine-azithromycin combinations for their in vitro and in vivo antimalarial properties. In vitro 96-h susceptibility testing of chloroquine-azithromycin combinations showed mostly additive interactions against freshly cultured P. falciparum field isolates obtained from Mali. Some evidence of synergy, however, was apparent at the fractional 90% inhibitory concentration level. Additional in vitro testing highlighted the resistance reversal properties of amlodipine for both chloroquine and quinine. In vivo experiments, using the Peters 4-day suppressive test in a P. yoelii mouse model, revealed up to 99.9% suppression of parasitemia following treatment with chloroquine-azithromycin plus the R enantiomer of amlodipine. This enantiomer was chosen because it does not manifest the cardiac toxicities observed with the racemic mixture. Pharmacokinetic/pharmacodynamic analyses in this rodent model and subsequent extrapolation to a 65-kg adult led to the estimation that 1.8 g daily of R-amlodipine would be required to achieve similar efficacy in humans, for whom this is likely an unsafe dose. While these data discount amlodipine as an additional partner for chloroquine-based combination therapy, our studies continue to support azithromycin as a safe and effective addition to antimalarial combination therapies.

The EXCITE (clinical EXperienCe of amlodIpine and valsarTan in hypErtension) study was designed to evaluate the effectiveness, tolerability and adherence of amlodipine/valsartan (Aml/Val) and amlodipine/ valsartan/hydrochlorothiazide (Aml/Val/HCT) single-pill combination therapies in patients with hypertension from the Middle East and Asia studied in routine clinical practice.

A high-pressure liquid chromatography (HPLC-UV) based simple and specific method for simultaneous quantitative determination of aspirin, amlodipine besylate and simvastatin in a capsule formulation has been developed and validated according to ICH guidelines. Chromatographic separation of the three drugs was carried out by aSpherisorbODS2 reverse phase column (4.6 x 250 mm; 5 μm) using amobile phase, which consisted of 70: 30 (v/v) mixture of acetonitrile and triethylamine phosphate buffer (pH 3; 0.015 M) with final pH adjusted to 2.5 using dilute ortho-phosphoric acid, at a flow rate of 1mL/min. The eluents were detected at UV wavelength of 237 nm and the retention times for aspirin, amlodipine besylate and simvastatin were ~2.7 mins, ~6.1 mins and ~10.5mins, respectively. This method is suitable and specific for the three drugs and was found to be linear (R2&gt;0.995), accurate, specific, reproducible and robust in the concentration range of 375 to 1125mcg/ml for aspirin, 25 to 75...

To study the efficacy and safety of a new combination of perindopril arginine and amlodipine besylate, 837 subjects were enrolled in a three-arm, prospective, 59-center, randomized clinical trial. For 42 days, subjects (average seated blood pressure [BP], 158 AE 12/101 AE 5 mm Hg; age, 52 AE 10 years; 52% male; 34% black; 20% diabetic) received amlodipine/ perindopril arginine (10/14 mg/d), perindopril erbumine (16 mg/d), or amlodipine (10 mg/d). Goal BP was <140/90 or <130/ 80 mm Hg in diabetics, per JNC 7 guidelines. The combination showed the largest change in seated BP (À23.7/À15.7 vs. À13.7/À9.5 vs. À19.3/À13.2 mm Hg, respectively; P < .0001), the highest proportion at goal BP (51% vs. 26% vs. 37%; P < .0001), and a lower incidence of pedal edema and adverse events compared with amlodipine. No deaths or significant differences across groups in early discontinuation, serum potassium, or rates of total or serious adverse events or glomerular filtration, were observed. J Am Soc Hypertens 2015;9(4):266-274. edema. Recent hypertension guidelines have recommended a trial of lifestyle modifications, with consideration of initiating drug therapy if BP is persistently !140/90 mm Hg, using an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker, calcium channel blocker,

ly to reach a target MAP of 107 mm Hg. The adjusted hazard ratio (AA/AG compared to GG) with 95% confidence interval was 3.41 (1.20-9.64; p = 0.020). Among participants randomized to a lower MAP goal, those with the C allele at CYP3A4 T16090C were more likely to reach target MAP: The adjusted hazard ratio was 2.04 (1.17-3.56; p = 0.010). After adjustment for multiple testing using a threshold significance level of p = 0.016, only the CYP3A4 T16090C SNP remained significant. CYP3A5 A6986G was not associated with blood pressure response. Conclusions: Our findings suggest that blood pressure response to amlodipine among high-risk African-Americans appears to be determined by CYP3A4 genotypes, and sex specificity may be an important consideration. Clinical applications of CYP3A4 genotype testing for individualized treatment regimens warrant further study.

Acute intermittent porphyria (AIP) is probably the most common of the genetic porphyrias . Drugs reported as unsafe in patients with porphyria include sulphonamides, erythromycin, barbiturates, hydantoins, carbamazepine, valproate, oestrogens, oral contraceptives, tricyclic antidepressants, benzodiazepines, calcium channel blockers [2] (especially nifedipine) and angiotensin-converting enzyme inhibitors (especially enalapril) . We report here a case of AIP where the patient used amlodipine for hypertension and was free from attacks.

The study describes development and subsequent validation of a stability indicating reverse-phase HPLC method for the simultaneous estimation of atorvastatin (ATV), and amlodipine (AML) from their combination drug product. The proposed RP-HPLC method utilizes a Lichrospher 100 C18, 5 microm, 250 mm x 4.0 mm i.d. column, at ambient temperature, optimum mobile phase consisted of acetonitrile and 50 mM potassium dihydrogen phosphate buffer (60 : 40, v/v), apparent pH adjusted to 3+/-0.1 with 10% phosphoric acid solution, effluent flow rate monitored at 1.0 ml/min, and UV detection at 254 nm. ATV, AML, and their combination drug product were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by proposed method. The method was applied for the in vitro dissolution of marketed combination drug products. The described method was linear over the range of 1-90 microg/ml and 1-80 microg/ml for ATV and AML, respectively. The mean recoveries were 99.76 and 98.12% for ATV and AML, respectively. The intermediate precision data obtained under different experimental setup, the calculated value of coefficient of variation (CV, %) was found to be less than critical value. The limit of detection for ATV and AML were found to be 0.4 and 0.6 mug/ml, respectively and the limit of quantification was 1.0 microg/ml for both drugs. The average percentage drug release was found to be more than 70% within 30 min for both drugs. Chromatographic peak purity data of ATV and AML indicated no co-eluting peaks with the main peaks of drugs which demonstrated the specificity of assay method for their estimation in presence of degradation products. The proposed method can be useful in the quality control and in vitro dissolution of combination drug products.

In this study a new simple, precise and accurate HPTLC method has been developed for simultaneous estimation ofOlmesartanmedoxomil, Amlodipine besylate and Hydrochlorothiazide in pharmaceutical dosage forms.
Chromatographic separation of the drugs was performed on precoated silica gel 60 F254 plates using Chloroform:Methanol: Formic acid (8.5:1.5:0.25, v/v/v). A TLC scanner set at 254 nm was used for the direct evaluation of the chromatogramin reflectance-absorbancemode. The drugswere satisfactorily resolved with Rf values of0.57 ± 0.02, 0.36 ± 0.04 and 0.21 ± 0.02 for Olmesartan medoxomil, Amlodipine besylate and Hydrochlorothiazide. The accuracy and reliability of the method was assessed by evaluation of linearity (200-2000 ng/spot for OLME, 50-500 ng/spot forAMLO and 125-1250 ng/spot for HCTZ), precision (intra-dayRSD0.4510%, inter-day RSD, 0.2773% and analyst to analyst RSD0.1959 for OLME, intra-dayRSD 1.0216%, inter-day RSD 0.3137%, analyst to analystRSD 0.8557%forAMLO) (intra-dayRSD 0.4117%, inter-day RSD 0.2974% and analyst to analyst RSD 0.2038% for
HCTZ, accuracy forOLME,AMLOandHCTZafford 98-102%and specificity in accordance with ICH guidelines. This HPTLC Method had the potential to determine these drugs simultaneously from dosage forms without anyinterference. 2013 Trade Science Inc. - INDIA

The aim of this meta-analysis was to compare the effi cacy and safety profi le of manidipine 20 mg with that of amlodipine 10 mg. A systematic research of quantitative data produced or published between 1995 and 2009 was performed. Headto-head randomized controlled trials (RCTs) of 12 months minimum duration reporting comparative effi cacy (changes in systolic and diastolic blood pressure) and safety (total adverse events and ankle oedema), were included. Four high-quality RCTs, accounting for 838 patients (436 received manidipine and 402 received amlodipine) were included. The effi cacy of manidipine and amlodipine was statistically equivalent: effect size for DBP ϭ Ϫ 0.08 ( p ϭ 0.22) and SBP ϭ Ϫ 0.01 ( p ϭ 0.83). The global safety of manidipine was signifi cantly better than amlodipine: the relative risk (RR) for adverse event was 0.69 (0.56 -0.85), and particularly for ankle oedema RR was 0.35 (0.22 -0.54). Publication bias was not signifi cant and the robustness of the analyses was good. These data suggest a better effi cacy/safety ratio of manidipine over amlodipine.

Aims: This study was conducted to assess the bioequivalence between two 10-mg amlodipine tablet formulations. As secondary objectives, sex-related differences and tolerability profile were evaluated. Methods: Thirty-six healthy volunteers (18 males and 18 females; age 20-32 years, weight 49.5-98.0 kg) were included in a randomised crossover study. Subjects were administered a single 10-mg oral dose of each formulation separated by a 14-day washout period. Plasma amlodipine levels were determined by a high performance liquid chromatographic method with tandem mass spectrometry detection. Results: All subjects completed the study and 90% confidence intervals for relevant pharmacokinetic parameters were within the ranges defined by European and US Regulatory Authorities: the geometric mean and the 90% confidence interval test/reference ratios calculated from log-transformed values were 104.54 (101.46-107.72%) for AUC 0-∞ and 100.32 (97.41-103.33%) for C max . There were no serious or severe adverse events. The tolerability profile appeared to be comparable for the two products. On average, bioavailability of amlodipine was slightly higher in females than in males, but these differences could be explained by the lower body weight of women. There were no sex-related differences in drug clearance. Bioequivalence was also demonstrated within each gender group. Amlodipine treatment produced a slight decrease of systolic blood pressure and an increased in heart rate, which were more pronounced in women. The incidence of adverse events was similar in men and women. Conclusions: The two formulations were considered bioequivalent. Although there were no relevant gender-related differences in the pharmacokinetics of amlodipine, women reached higher amlodipine concentrations most likely because of their lower body weight, and therefore, the reported pharmacodynamic effects were higher within this gender group.