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Bisoprolol and Hydrochlorothiazide [keywords]
- Bioequivalence Study of 2 Formulations of Film-coated Tablets containing a Fixed Dose Combination of Bisoprolol Fumarate 5 mg and Hydrochlorothiazide 6.25 mg in Healthy Subjects. [JOURNAL ARTICLE]
- Drug Res (Stuttg) 2013 Mar 28.
The present study was conducted to compare the bioavailability of 2 formulations of fixed-dose combination of bisoprolol fumarate 5 mg and hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (test and reference formulations).This study was a randomized, single-blind, 2-period, 2-sequence cross-over study which included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters, AUCt, AUCinf, Cmax, tmax, and t½ were determined based on the concentrations of bisoprolol (CAS 66722-44-9) and HCT (CAS 58-93-5), using ultra-performance liquid chromatography with tandem mass spectrometer detector (UPLC-MS/MS). In each of the 2 study periods (with a washout of 1 week) a single dose of test or reference product was administered.The geometric mean ratios (90% CI) of the test drug/reference drug for bisoprolol were 97.22% (93.75-100.83%) for AUCt(0-48), 97.20% (93.97-100.54%) for AUCinf, and 100.36% (93.83-107.34%) for Cmax; while those for HCT were 93.22% (84.72-102.57%), 93.39% (85.43-102.10%) and 99.39% (85.45-115.61%), for AUCt(0-24), AUCinf, and Cmax, respectively. The differences between the test and reference drug products for tmax values of bisoprolol as well as t½ values of both bisoprolol and hydrochlorothiazide were not statistically significant; yet, the difference was statistically significant for the tmax values of hydrochlorothiazide. There was no adverse event encountered during this bioequivalence test.It was concluded that the 2 formulations of fixed dose combination of bisoprolol fumarate 5 mg and hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (the test and reference products) were bioequivalent.
- Fully validated simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in their dosage forms using different voltammetric, chromatographic, and spectrophotometric analytical methods. [Journal Article, Validation Studies]
- J AOAC Int 2013 Jan-Feb; 96(1):42-51.
Voltammetric, chromatographic, and spectrophotometric methods were developed for the simultaneous determination of bisoprolol fumarate (BIS) and hydrochlorothiazide (HCZ). Differential pulse and square wave voltammetry techniques were used to analyze BIS and HCZ simultaneously by measuring at about 1400 and 1100 mV, respectively. RP-HPLC was the second method for simultaneous analysis of the compounds. The mixture of BIS, HCZ, and moxifloxacin as an internal standard was separated on an RP Zorbax Eclipse XDB-C18 column (150 x 4.6 mm, id, 5 microm particle size) using acetonitrile-15 mM phosphate (25+75, v/v) mobile phase at a 1.0 mL/min flow rate. The third method was based on first derivative of the ratio-spectra method obtained from the measurements of the amplitudes at 246 and 257 nm for BIS and HCZ, respectively. All the proposed methods were effectively applied for the simultaneous determination of BIS and HCZ in tablet dosage forms without any time-consuming extraction, sample preparation, or derivatization procedures.
- [Telangiectasia during amlodipine therapy]. [English Abstract, Journal Article]
- Ann Dermatol Venereol 2013 Mar; 140(3):202-5.
Calcium inhibitors are recommended as first-line treatment in hypertension. We report the development of telangiectasia on the trunk and upper limbs in a female patient on amlodipine (Amlor(®)) that subsided on treatment discontinuation.A 63-year-old woman consulted for numerous asymptomatic stellate telangiectasias on her upper trunk and shoulders, with sparing of the face. No Darier's sign was seen and clinical examination was otherwise normal. The patient had been treated with amlodipine (Amlor(®)) and a combination of bisoprolol and hydrochlorothiazide (Lodoz(®)) for 5years for essential hypertension. Laboratory tests, which included serum tryptase assay, were normal. Histological analysis showed a normal epidermis with dilated superficial dermal capillaries and no inflammatory infiltrate or dermal elastosis. Amlodipine was discontinued and replaced with ramipril (an ACE inhibitor). The other treatments were changed over and the telangiectasias regressed spontaneously within several months, with no relapse being seen at one year of follow-up.Reports of telangiectasia associated with calcium inhibitors most commonly involve the dihydropyridine family, of which amlodipine is a member. Inhibition of muscular contraction induced by this treatment results in vasodilatation, accounting for the associated antihypertensive properties, and this could play a role in telangiectasia formation. The literature contains reports of cases of photo-distributed telangiectasia, suggesting that as well as vasodilatation, calcium inhibitors may in certain cases cause abnormal sensitivity of blood vessels to ultraviolet radiation. The absence of facial lesions rules out the hypothesis of photo-induced lesions in our patient.
- Monitoring drug residues in donor blood/plasma samples using LC-(MS)/MS - a pilot study. [LETTER]
- Drug Test Anal 2013 Jan 21.
Quality assurance of pharmaceutical products is of particular importance and thoroughly controlled. Among these, the preparation of human plasma follows strict guidelines from the point of donor selection to product processing. While various precautions particularly concerning antiviral treatment as well as quality assessment are standard procedure, tests for drug residues are rarely, if at all, conducted with fresh frozen plasma products. With the constantly increasing sensitivity and specificity of modern analytical instruments, the detection of trace amounts of therapeutics in plasma is feasible and can be applied to blood products where considered appropriate. To estimate the prevalence of a selection of commonly prescribed and over-the-counter drugs (including diuretics, beta-receptor blocking agents, contraceptives, β(2) -agonists, antibiotics, antidepressants, analgesics, opioids, glucocorticosteroids, benzodiazepines, stimulants, and oral anti-diabetics) as well as cannabinoids in human donor plasma, a total of 100 specimens (61 female, 39 male) collected at the German Red Cross Organization in 2012 was subjected to an established analytical approach. The methodology was based on protein precipitation followed by liquid chromatographic-high resolution/high accuracy mass spectrometric analysis. Following initial test results, confirmatory analyses were conducted with respective reference substances employing a conventional liquid chromatography-triple-quadrupole mass spectrometer (LC-MS/MS) apparatus. Out of one hundred samples, five were found to contain diuretics (four hydrochlorothiazide and one torasemide), five contained beta-receptor blocking agents (four bisoprolol and one metoprolol), one was found with residues of pseudoephedrine (stimulant) and one with drosperinone (contraceptive). Overall, 12% of samples yielded detectable amounts of drug residues at concentrations estimated to levels common to individuals under therapeutic treatment. In addition, six aliquots of different lots of commercially available plasma preparations with solvent-detergent processing were tested. Here, no drug residues of the targeted therapeutics were detected. Copyright © 2013 John Wiley & Sons, Ltd.
- Simultaneous acquisition of the dissolution curves of two active ingredients in a binary pharmaceutical association, employing an on-line circulation system and chemometrics-assistance. [Journal Article, Research Support, Non-U.S. Gov't]
- J Pharm Biomed Anal 2013 Jan.:51-8.
The association of an on-line circulation system with a chemometrics-assisted UV detection strategy is described as a useful system to continuously monitor the dissolution of a pharmaceutical preparation containing two active ingredients, and as a tool for the simultaneous determination of the dissolution curves and dissolution profiles of the latter. Multivariate curve resolution with alternating least squares (MCR-ALS) was used as the chemometric tool to quantitate the analytes, while the hydrochlorothiazide-bisoprolol fumarate (HCT-BIS) association was employed as a model for method development. The experiments were carried out with a dissolution tester configured as apparatus II (paddles), under USP 32 official conditions. The suitability of the calibration procedure for quantitating the dissolved drugs was assessed according to ICH guidelines, with regards to linearity in the working range, specificity, accuracy and precision. Figures of merit, including limits of detection and quantitation were also determined, as well as the method's robustness with regards to detection wavelength range. The system was able to consistently provide very reproducible dissolution curves of commercial tablets, which were statistically similar to those furnished by a manual sampling technique, followed by HPLC analysis. To demonstrate the usefulness of the proposed system, the dissolution profiles of different lots of HCT-BIS tablets were acquired and three of them were conveniently compared at a 31 data point level, employing the f(1) and f(2) ("difference" and "similarity") indexes. Use of multiple data points for comparison ensured reliability of the results.
- Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study. [Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't]
- J Hypertens 2012 Aug; 30(8):1656-64.
To compare two drug regimens to treat resistant hypertension.In a prospective, randomized, open blinded endpoint study, 167 patients with mean baseline daytime ambulatory blood pressure 135 mmHg or more and/or 85 mmHg or more, despite 4 weeks' treatment with irbesartan 300 mg/day, hydrochlorothiazide 12.5 mg/day and amlodipine 5 mg/day, were randomized to sequential nephron blockade (group 1, n = 85) or sequential renin-angiotensin system blockade (group 2, n = 82). First, spironolactone 25 mg/day in group 1 or ramipril 5 mg/day in group 2 were added for 4 weeks. Treatment was increased at weeks 4, 8 or 10 if home blood pressure was 135 mmHg or more and/or 85 mmHg or more by sequentially administering furosemide 20 mg/day, furosemide 40 mg/day and amiloride 5 mg/day in group 1, or ramipril 10 mg/day, bisoprolol 5 mg/day and bisoprolol 10 mg/day in group 2. The primary endpoint was change in systolic daytime ambulatory blood pressure at week 12.At week 12, the mean between-group difference in daytime ambulatory blood pressure was 10/4 mmHg (95% confidence interval: 7-14/2-7; P < 0.001/P = 0.0014) in favour of the group 1. The blood pressure goal (daytime ambulatory blood pressure <135/85 mmHg) was achieved in 58% in the group 1 and 20% in the group 2 (P < 0.0001). Discontinuation for drug-related adverse events was low (group 1, n = 7; group 2, n = 6).In patients with resistant hypertension, sequential nephron blockade induces a large and well tolerated reduction in blood pressure via a progressive increase in sodium depletion, and is more effective than sequential renin-angiotensin system blockade.
- Clinical and molecular approaches to individualize antihypertensive drug therapy. [Journal Article, Review]
- Ann Med 2012 Jun.:S23-9.
Interindividual variation of blood pressure (BP) responses to antihypertensive drugs is extensive. Several clinical, laboratory, and genetic predictors of BP responses to blood pressure-lowering agents have been suggested. We describe here the principal findings from the GENRES Study which is primarily a pharmacogenetic study of antihypertensive drug responses but also includes analysis of certain clinical and laboratory predictors. In this placebo-controlled, double-blinded, and randomized study, more than 200 male subjects with essential hypertension were treated with four antihypertensive drug monotherapies (amlodipine, bisoprolol, hydrochlorothiazide, and losartan) in a cross-over fashion, resulting in more than 800 treatment periods. Generally, placebo BP level was the best predictor of BP responses. In addition, higher baseline plasma renin activity predicted better BP response to losartan and bisoprolol, and weaker response to hydrochlorothiazide. A number of candidate gene polymorphisms analysed so far have given negative results in relation to BP responses, with the exception of an STK39 variant associating with losartan responsiveness. In future, genome-wide association studies on antihypertensive pharmacogenetics may identify novel pathways of BP regulation and provide new tools for both basic research and clinical use.
- Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients. [Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't]
- Trials 2012.:59.
The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa.At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study.NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.
- Palatability of crushed ß-blockers, converting enzyme inhibitors and thiazides. [Journal Article, Randomized Controlled Trial]
- J Clin Pharm Ther 2012 Oct; 37(5):544-6.
WHAT IS KNOWN AND OBJECTIVES: A problem that often affects antihypertensive drugs is the lack of formulations appropriate for childhood. Parents, therefore, crush tablets and administer the antihypertensive drug mixed with solid food or a palatable drink. Because palatability is a major modulator of adherence to prescribed medication, the palatability of crushed ß-blockers, converting enzyme inhibitors and thiazides was assessed among adult volunteers.The palatability of crushed atenolol, bisoprolol, enalapril, lisinopril, ramipril, chlorthalidone and hydrochlorothiazide was evaluated by means of a facial hedonic scale among 20 volunteers. The calcium channel-blockers amlodipine and lercanidipine whose tastes are disliked and liked, respectively, by children were also tested. A concealed random allocation procedure was used.The palatability scores assigned to chlorthalidone, hydrochlorothiazide and lisinopril were superior (P < 0·002) to those assigned to atenolol, bisoprolol, enalapril and ramipril. As with children, the palatability score of lercanidipine was superior to that of amlodipine (P < 0·002). The scores assigned to the various agents were similar in women and in men and were age-independent.Pulverized atenolol, bisoprolol, enalapril and ramipril are poor tasting. From the perspective of palatability, pulverized chlorthalidone, hydrochlorothiazide and lisinopril are preferable.
- [Combined low-dose antihypertensive therapy in pregnant women with hypertension and preeclampsia]. [English Abstract, Journal Article]
- Kardiologiia 2012; 52(1):32-8.
The effect of low-dose combination antihypertensive therapy in fixed form, containing 2.5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide, the clinical condition, the daily profile of blood pressure, body adrenoreactivity structural and functional parameters of the left ventricle in 28 pregnant women with preeclampsia in the background chronic hypertension (hypertension stage II, 2 nd degree) and 28 pregnant women with preeclampsia and mild to moderate severity in terms of 22-28 weeks of pregnancy. After 16 weeks of receiving a fixed form, containing 2.5 mg of bisoprolol and 6.25 mg hydrochlorothiazide, the target BP level reached 76% of pregnant women with preeclampsia with chronic hypertension and 81% - with preeclampsia. In both groups, the parameters are optimized daily profile of blood pressure, the value of the total peripheral vascular resistance.