Combination Of Chlorthalidone Research Articles

Eco-friendly based HPLC and UV-spectrophotometric methods for simultaneous estimation of Efonidipine hydrochloride Ethanolate and Chlorthalidone in their dosage form

ObjectiveEfonidipine hydrochloride Ethanolate and Chlorthalidone combination was approved by CDSCO for Phase III clinical trial. This combination is utilized to pharmacological therapy that can effectively control hypertension situations. The present research includes an RP-HPLC and Simultaneous equation UV methods for the determination of drug combination in tablet dosage form. Furthermore, greenness assessment and statistical evaluation of developed methods. MethodsThe HPLC chromatography was performed using a gradient technique on a reversed-phase C18 column with mobile phase based and optimized depending on the polarity of the molecules. The Unesphere C18 column Agela Tech., (250 mm x 4.6 mm i.d, 5 μm,) as stationary phase and Acetonitrile: 0.2 M Potassium dihydrogen orthophosphate pH 4 (68: 32% v/v) as mobile phase. The Simultaneous equation UV method was developed and validated at 220 nm and 250 nm in methanol: distilled water (20:80, v/v). The greenness assessment tools were used to assess the ecological impact of the new UV spectrophotometric method and HPLC method. ResultsUV detection in RP-HPLC method at 220 nm for gradient elution was used to achieve chromatographic separation over the linearity 3.0–60.0 μg/mL and 10.0 - 200.0 μg/mL and for UV method 3.0–15.0 μg/mL and 10.0–50.0 μg/mL for Chlorthalidone (CLT) and Efonidipine (EFD) respectively.The value of% RSD within the limit indicated that the method is precise, accurate and% recovery shows that there is no interference from the excipients.Greenness assessment data confirmed the method's environmental friendliness in terms of solvent usage, chemical compounds, energy consumption, and trash creation. There were no spectral or chromatographic interferences from formulation excipients discovered. ConclusionThe analytical method validation parameters were found to be as per acceptance criteria. In terms of accuracy and precision, statistical testing employing an analysis of variance test did not find any significant differences between the two methods. To evaluate the greenness and whiteness of an analytical method, a reliable assessment of the health and environmental risk associated with chemical use is essential.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial.

To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5mg of chlorthalidone/amiloride (N = 47) or 50mg of losartan (N = 50), and followed for 18months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10mg) and propranolol (40 and 80mg BID) were added as open label drugs in a progressive fashion. Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18months of follow-up, systolic BP was 128.4 ± 10.3mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. Clinical trials registration number: NCT00971165.

Stability Indicating Method to Analyze Benidipine and Chlorthalidone Using HPLC Technique: Establishment, Validation and Application to Tablets

Background : The combination of chlorthalidone and benidipine was used to manage hypertension. The mixture of chlorthalidone and benidipine in tablet dosage form has not been previously determined by any method. A stability indicating HPLC method was developed for the simultaneous determination of benidipine and chlorthalidone in bulk and tablets. Methods: Chromatographic separation was accomplished in a reverse phase system using an isocratic elution with a mobile phase composed of methanol-0.1M dipotassium hydrogen phosphate buffer (40:60, v/v), at 1 ml/min flow rate. The photodiode array (PDA) detector set at 260 nm was used to detect and quantify benidipine and chlorthalidone. Benidipine and chlorthalidone tablet samples were subjected to degradation under acid, neutral, alkali, thermal, photo and oxidative. The proposed method was effectively adapted to quantify benidipine and chlorthalidone in the combined tablet formulation. Results: The elution times for benidipine and chlorthalidone were approximately 4.573 min and 6.422 min, respectively. The method was validated within a concentration range of 2 - 6 μg/ml (R2 = 0.9997) for benidipine and 6.25 - 18.75 μg/ml (R2 = 0.9998) for chlorthalidone. Adequate results were obtained for precision (RSD% = 0.106% for benidipine and RSD% = 0.031% for chlorthalidone) and accuracy (99.95 - 100.25 % mean recovery for benidipine and 99.60 - 99.63% mean recovery for chlorthalidone). Robustness has also been found to be acceptable. During the degradation study, interference was not noticed in the analysis of studied drugs. Conclusion: The findings demonstrated that the method could be useful for determination of the selected drug combination in routine analysis.

An observational comparative study of different doses of azilsartan and with chlorthalidone combination in moderate hypertension

Background: High blood pressure (BP) is one of the significant non-communicable diseases that are of high prevalence in our country. Hypertension (HTN) is responsible cause of 57% of stroke and 24% of coronary heart disease deaths in India. Eight classes of medications are currently used in the treatment of hypertension. Azilsartan medoxomil is a newly added FDA approved drug to the ARB class of antihypertensive agents. azilsartan and chlorthalidone combination is also got the FDA approval. There is limited study in between these two groups regarding efficacy especially in rural Bengal.Methods: A prospective observational study was done in medicine OPD of Bankura Sammilani Medical College for twelve weeks with two groups that are azilsartan (80mg) and fixed dose combination of azilsartan (40mg) plus chlorthalidone (12.5mg) in the age group of 18 to 55years of moderate hypertensive patients. Change of heart rate was assessed as safety parameter.Results: It was found that both the group of drugs are very much effective in lowering blood pressure constantly in respect of both systolic and diastolic BP but azilsartan monotherapy in high dose reduce systolic blood pressure slightly high. Significant change of heart rate was not seen with both the groups.Conclusions: Both the group was effective as well as safe in hypertensive patients.

A prospective and open label study of use of cilnidipine and chlorthalidone fixed dose combination in Indian hypertensive patients, intolerant or uncontrolled on amlodipine and hydrochlorothiazide combination

Background:Primary aim of this study was to evaluate the antihypertensive efficacy of the Cilnidipine and Chlorthalidone fixed dose combination in Indian hypertensive patients who are not controlled on traditionally used amlodipine and hydrochlorothiazide combination and also to evaluate the safety of this combination.Methods: A total of 70 eligible patients were enrolled in this prospective, open label study. The patients were given cilnidipine (10 mg) and chlorthalidone (12.5 mg) who had not achieved target blood pressure (140/90 mmHg) despite on amlodipine (5 mg) and hydrochlorothiazide (12.5mg) combination or are intolerant to the medication. The assessment was done at the end of 4 weeks and 8 weeks.Results: There were significant falls in the SBP (5.43±2.45 mmHg, P&lt;0.05), and DBP (4.11±2.35 mmHg, P&lt;0.05) at the end of 4 weeks as compared to those at the baseline. The trend was sustained at 8 weeks. No further significant fall in the SBP and DBP were noted after 4 weeks (5.43±2.45 and 5.22±2.38 mmHg at 4 weeks vs 4.11±2.35 and 4.01±2.23 mmHg at 8 weeks P=NS). The SBP target (140 mmHg) was achieved in 25 patients (35.71%). The DBP target (90 mmHg) was achieved in 18 patients (25.71%). The combined SBP and DBP target was achieved in 12 patients (17.14%). A similar fall in the SBP was observed in the subgroups which were analysed.Conclusions: The hypertensive patients who do not achieve the target blood pressures on amlodipine and hydrochlorothiazide can be switched to the cilnidipine and chlorthalidone combination. The combination is effective and well tolerated.

Evaluation of Efficacy and Safety of Oral Olmesartan+ Chlorthalidone Combination in the Management of Hypertension in Indian Patients

Hypertension is the most prevalent chronic disease in India and its prevalence is rapidly increasing among urban and rural populations. Reducing blood pressure can decrease cardiovascular risk and all cause mortality. This study was conducted to assess the efficacy and safety of fixed dose combination of Olmesartan 40 mg and Chlorthalidone12.5mg. 30 hypertensive patients having systolic blood pressure ? 160 mmHg and diastolic blood pressure ?100 mmHg who were uncontrolled on monotherapy with olmesartan were enrolled in this study. The treatment period was of 60 days and patients were administered once daily fixed dose combination of Olmesartan40 mg and Chlorthalidone 12.5 mg. Patients were evaluated on 15th, 30th and 60th days of treatment.There was statistically significant (p&lt;0.0001) decrease in systolic blood pressure from baseline to 15th, 30th and 60thday of treatmentmean±SD (179.1±13.38 mmHg vs. 169.3±13.05, 154.3±13.31, and 142.7±6.91mmHg) respectively. Similarly the diastolic blood pressure (DBP) was significantly (p&lt;0.0001) reduced from the baseline to the 15th, 30th and 60thday of treatment (94.97±5.75mmHg vs.86.67±4.79, 80.33±1.82 and 76.7±4.32 mmHg respectively). Thus fixed dose combination of Olmesartan and Chlorthalidonewas found to be effective and safe option for the optimal management of hypertension.J MEDICINE January 2017; 18 (1) : 6-9

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.

To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 333) or 50 mg of losartan (N = 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 ± 40.4 versus 16.2 ± 26.7 mg, P = 0.09). Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. NCT00971165.

The Antihypertensive Efficacy of Chlorthalidone and Telmisartan in Indian Hypertensive Patients who were Uncontrolled with Hydrochlorothiazide and Telmisartan Combination-A Prospective and an Open Label Study

The primary objective of this study was to evaluate the antihypertensive efficacy of the chlorthalidone and telmisartan combination in Indian hypertensive patients who remained uncontrolled after taking the hydrochlorothiazide and telmisartan combination. A total of 100 eligible patients were enrolled in this prospective, open label study. The patients were given telmisartan (40 mg) and chlorthalidone (12.5 mg), who had not achieved the target blood pressure (140/90 mmHg) despite taking the combination of telmisartan (40 mg) and hydrochlorothiazide (12.5 mg). The assessment was done at the end of 4 weeks and 8 weeks. The mean SBP and DBP after taking telmisartan (40 mg) and hydrochlorothiazide (12.5 mg) were 154.88±9.57 (range 144 to 160) mmHg and 99.37±2.78 (range 92 to 106). At the end of 4 weeks of being on telmisartan (40 mg) and chlorthalidone (12.5 mg), the mean SBP and DBP were 145.56±5.12 (range 134 to 158) mmHg and 95.14±4.27 (range 84 to 100) mmHg. Significant falls in the SBP (5.32±2.64) and DBP (4.18±2.48) were noted at the end of the 4 week therapy. They were sustained at the end of 8 weeks also. The SBP target (<140 mmHg) was achieved in 24 % patients. The DBP target (<90 mmHg) was achieved in 19% patients. The combined SBP and DBP target (<140/90 mmHg) was achieved in 15% patients. No significant clinical adverse events were reported. Similar falls in the SBP and DBP were noted in the subgroups (smokers, females, diabetics, etc). The hypertensive patients who do not achieve the target blood pressures on telmisartan and hydrochlorothiazide can be switched on to the telmisartan and chlorthalidone combination. This combination is effective and well tolerated.

Newer renin–angiotensin–aldosterone system blocker combinations

The necessity for new and more effective management approaches to achieve blood pressure goals is still present in spite of the number of antihypertensive medications available. One of the cornerstones of successful therapy is implementation of drug combinations that act on complementary biological pathways. This review article focuses on the evaluation of recent data supporting newer combinations involving inhibition of the renin-angiotensin-aldosterone system (RAAS) with other drug classes such as calcium channel blockers (CCBs) and diuretics. New angiotensin receptor blockers as well as renin inhibitors, with a more robust blood pressure-lowering effect than their predecessors, have emerged recently. The data presented in this text also strongly supports a combination therapy approach as initial therapy to achieve blood pressure goals in a timely fashion. Additionally, the blood pressure-lowering effect is more robust with lower-dose, single-pill combinations than with highest doses of single agents alone. Therefore, using combination agents is less prone to side effects. The challenges for such single-pill combinations remain affordability. For this reason, payers and patients have traditionally not preferred such agents in spite of better blood pressure control and adherence rates. The new combinations of renin inhibitors and the new angiotensin receptor blocker combinations add to the armamentarium of agents to control blood pressure. Whereas the new angiotensin receptor blocker offers greater efficacy on blood pressure control over other agents in the class and the availability of the only chlorthalidone combination, no outcome data exist yet with any of the new agents.

The Choice of Thiazide Diuretics

Thiazide diuretics were introduced in the United States for the treatment of hypertension in 1957. The first of these, chlorothiazide, was soon accompanied by a large number of other sulfonamide derivatives, including chlorthalidone. Hydrochlorothiazide (HCTZ) rapidly became the most commonly prescribed antihypertensive drug in the United States, whereas bendroflumethiazide was most popular in the United Kingdom. The initial popularity of HCTZ in the United States was abetted by its use in the first controlled trial of the treatment of nonmalignant hypertension, the Veterans’ Affairs Cooperative Study.1 The starting dose of HCTZ was 50 mg/d, and it was used along with reserpine and hydralazine. A number of other trials published in the 1970s all used higher doses of diuretic, for example, ≥50 mg of HCTZ per day.2 For reasons unknown to me, chlorthalidone was chosen to be the diuretic in the first large controlled trial of the treatment of hypertension, the Hypertension Detection and Follow-Up Program.3 In the Hypertension Detection and Follow-Up Program, all 10 940 patients were started on chlorthalidone from 25 to 100 mg/d. Other drugs were added to achieve control of the blood pressure. In addition, half were assigned to “referred” care and the other half to more closely monitored and intensively treated “stepped” care. The stepped care–treated half achieved a 4.4% further reduction in diastolic blood pressure and a 17.0% reduction …

Validated HPLC Method for the Pharmacokinetic Study of Atenolol and Chlorthalidone Combination Therapy in Korean Subjects

A rapid, selective and sensitive reverse-phase HPLC methods for the determination of atenolol and chlorthalidone in human serum and whole blood were validated, and applied to the pharmacokinetic study of atenolol and chlorthalidone combination therapy. Atenolol and an internal standard, pindolol, were extracted from human serum by liquid-liquid extraction, and analyzed on a -Bondapak C18 column in a mobile phase of methanol-0.01 M potassium dihydrogenphosphate(30:70, v/v, adjusted to pH 3.5) and fluorescence detection(emission: 300 nm, excitation: 224 nm). Chlorthalidone and an internal standard, probenecid, were extracted form human whole blood by liquid-liquid extraction, and analyzed on a Luna C18 column in a mobile phase of acetonitrile containing 77% 0.01 M sodium acetate and UV detection at 214 nm. These analysis were performed at three different laboratories using the same quality control(QC) samples. The chromatograms showed good resolution, sensitivity, and no interference by human serum and whole blood, respectively. The methods showed linear responses over a concentration range of 10-1,000 ng/mL for atenolol and 0.05-20 for chlorthalidone, with correlation coefficients of greater than 0.999 at all the three laboratories. Intra- and inter-day assay precision and accuracy fulfilled international requirements. Stability studies(freeze-thaw, short-, long-term, extracted sample and stock solution) showed that atenolol and chlorthalidone were stable. The lower limit of quantitation of atenolol and chlorthalidone were 10 ng/mL and 0.05 , respectively, which was sensitive enough for pharmacokinetic studies. These methods were applied to the pharmacokinetic study of atenolol and chlorthalidone in human volunteers following a single oral administration of Hyundai tablet(atenolol 50 mg and chlorthalidone 12.5 mg) at three different laboratories.

The Combination of Chlorthalidone with Nifedipine Does Not Exert an Additive Antihypertensive Effect in Essential Hypertensives

To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, received, according to a randomized, double-blind, crossover design, nifedipine (20 mg b.i.d.), chlorthalidone (25 mg o.d.), the two drugs combined at the same doses, and the corresponding placebo. When compared to the randomized placebo the three active treatments significantly (p less than 0.001) reduced blood pressure without changing heart rate and body weight. However, blood pressure values were similarly reduced under nifedipine and the combination and were significantly lower (p less than 0.05) than those under chlorthalidone. Moreover, the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly (normalized, p less than 0.0001; responders, p less than 0.02) greater than those under chlorthalidone. Under chlorthalidone and its combination with nifedipine, plasma potassium tended to decrease and blood glucose and serum uric acid were significantly (p less than 0.05) increased. These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid. Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives.

A Combination of Chlorthalidone (12.5mg) and Atenolol (50mg) in the Elderly

A Combination of Chlorthalidone (12.5mg) and Atenolol (50mg) in the Elderly

Echocardiographic assessment of the effect of an antihypertensive regimen on left ventricular performance

A regimen consisting of chlorthalidone, hydralazine and propranolol would be useful in some hypertensive patients with coronary artery disease or aortic dissection if it could be shown that reflex cardiac stimulation induced by hydralazine is completely neutralized by propranolol. Nine hypertensive patients were treated with chlorthalidone during week 1, chlorthalidone and hydralazine during week 2 and a combination of chlorthalidone, hydralazine and propranolol during week 3. Blood pressure, heart rate, mean velocity of circumferential fiber shortening (V CF) measured echocardiographically and plasma renin activity were measured weekly. This potent three drug regimen reduced mean blood pressure from 142 to 102 mm Hg, and with the third drug, propranolol, heart rate, V CF and plasma renin activity returned to control levels from the greater elevated levels produced by the diuretic drug and hydralazine. In six additional patients V CF (an index of left ventricular contractility) was found to be proportionate to the rate of rise of aortic pressure ( dP dt ) or aortic shearing force. This regimen appears safe for use in patients with ischemic heart disease and aortic dissection.

Hypertensive vascular disease: The long term effect of rapid repeated reductions of arterial pressure with diazoxide ∗

The long term effect of repeated acute reductions of arterial pressure has been evaluated in 16 patients with severe hypertension who had become unresponsive to antihypertensive therapy. During a 20 day period, 300 mg. of diazoxide was administered intravenously and repeated on a daily basis as often as necessary to keep the arterial pressure more than 20 per cent below control levels. At the end of the 20 day period diazoxide had been successful in reducing the arterial pressure in 14 of 16 patients. In addition, retinopathy had cleared in 2, cardiac size significantly decreased in 4 and congestive heart failure had lessened in 4 and completely cleared in one patient. All 14 patients were then restarted on a combination of chlorthalidone and reserpine. Cardiovascular-renal function continued to improve with this therapy over a 30 month period in 7 patients. In the remaining 7 patients the addition of hydralazine or methyldopa administered in one-half the previous effective dose was needed to maintain the beneficial effect. Thirty months after the rapid reduction of arterial pressure, the average mean arterial pressure in the 14 patients was 123 + 6.7, compared to 112.5 ± 11.7 mm. Hg immediately after diazoxide. Retinopathy and congestive heart failure had cleared, and heart size was reduced in all patients. Since rapid reduction of arterial pressure with diazoxide was accomplished effectively, safely and in a short period of time, and since, at least in 14 of 16 patients studied here, beneficial effects were observed as long as 30 months it would seem: (1) that such aggressive therapy might be incorporated into the routine of treating patients with severe hypertension, and (2) the usefulness of such an approach might be evaluated in the therapy of patients with less severe types of hypertension.

The Role of Postganglionic Sympathetic Blockade in Antihypertensive Therapy

Currently, neurogenic blockade is used as a supplement to sulfonamide-diuretics (with or without reserpine) when optimal antihypertensive control is not obtained with these drugs alone. Although the use of neurogenic blocking agents preceded that of sulfonamide-diuretics by ten years, the latter have become first in therapeutic choice. A combination of chlorthalidone and reserpine produced normotension in 58 of 100 ambulatory outpatients with moderate to severe essential hypertension. Twentytwo of 42 subjects with residual hypertension became normotensive when chlorthalidone-reserpine therapy was augmented with a postganglionic sympathetic blocking agent (debrisoquin sulfate). In the authors' opinion neurogenic blocking agents, or other potent antihypertensive drugs as adjuncts to sulfonamide-diuretics, are indicated in approximately 40% of patients with moderate or severe essential hypertension. Debrisoquin appears to be more practical, as a supplementary antihypertensive drug, than older related blocking agents.