Bisoprolol and Hydrochlorothiazide [keywords]
- How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure. [Journal Article, Review]
- Front Physiol 2016.:320.
Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the long-term renal actions of antihypertensive agents in human studies and find three different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, some Ca(++)-channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors). These findings provide insights into the actions of antihypertensive drugs, and challenge misconceptions about the mechanisms underlying the therapeutic efficacy of many of the agents.
- Micellar Electrokinetic Chromatography (MEKC) with Multiresponse Chemometric Optimization for the Determination of Hydrochlorothiazide and Coformulated Antihypertensives in the Presence of Hydrochlorothiazide Major Impurity. [Journal Article]
- J Chromatogr Sci 2016 Jul; 54(6):1050-60.
In this work, micellar electrokinetic chromatographic method was developed and optimized for the determination of hydrochlorothiazide (HCT) in the presence of irbesartan (IRB), bisoprolol (BISO) and HCT main impurity. Four factors affecting the separation-sodium dodecyl sulphate (SDS) concentration, buffer concentration, temperature and voltage-were studied. Optimization studies were performed with the aid of a central composite design with six central points. The optimal separation conditions were obtained by applying Derringer's desirability function, and the conditions were borate buffer 17 mM (pH = 9), SDS 5.2 mM, temperature 25°C and voltage 12 kV. HCT, IRB and BISO were successfully determined in their pure form and pharmaceutical formulations with separation in <8 min. Calibration curves (R > 0.999) were prepared and complete method validation was performed according to ICH guidelines. The results obtained were statistically compared with that of the official methods.
- Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods. [Journal Article]
- J Pharm Biomed Anal 2016 May 30.:246-53.
Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes.
- [The influence of antihypertensive treatment on arterial stiffness, shear stress and activity of chosen matrix metalloproteinases]. [English Abstract, Journal Article, Randomized Controlled Trial]
- Przegl Lek 2015; 72(2):53-9.
The aim of the study was to compare therapeutic effects of chosen antihypertensive drugs on arterial stiffness, shear stress in carotid arteries and metalloproteinases activity, moreover analysis of relationship of these variables in the course of treatment.95 patients with essential arterial hypertension stage 1 or 2 were randomized to 6 months monotherapy with: quinapril, amlodipine, hydrochlorothiazide, losartan or bisoprolol. Each therapeutic group consisted of 19 patients (N=19). Before and then after 1, 3 and 6 months of treatment carotid-femoral pulse wave velocity (PWV) by using a Complior device, ultrasound of carotid arteries were performed. Blood samples for the measurement of whole blood viscosity were taken during each visit. Shear stress (SS) was calculated using measured variables: blood viscosity and velocity of blood flow. Serum concentration of metalloproteinase 3 (MMP-3) and plasma concentration of tissue inhibitor of metalloproteinase I (TIMP-1) were measured at the initial visit and after 6 months of treatment.ANOVA for repeated measurements revealed for all groups significant decrease of PWV (ΔPWV) and MMP-3 (ΔMMP-3) concentration and increase of shear stress in carotid artery and TIMP-1 (ΔTIMP-1) concentration (p<0.05). No between groups differences appeared in above effects (p>0.05). The multiple regression analysis for the change of PWV (ΔPWV) in the study group considering all investigated variables at R2 = 0,27 revealed its significant relation to PWV at first visit, ΔTIMP-1, ΔMMP-3 and Δ shear stress counted for the maximum flow velocity in common carotid artery. Conclusion: Irrespectively of chosen drug we observed similar effect for PWV drop. Reduction of arterial stiffness as a result of antihypertensive therapy is strongly connected with shear stress increase that is secondary to blood flow velocity growth and changes in connective tissue metabolism.
- PTPRD gene associated with blood pressure response to atenolol and resistant hypertension. [Journal Article]
- J Hypertens 2015 Nov; 33(11):2278-85.
The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol.Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n = 2114).In whites, two polymorphisms near the gene PTPRD (rs12346562 and rs1104514) were associated with DBP response to atenolol (P = 3.2 × 10 and P = 5.9 × 10, respectively) with directionally opposite association for response to hydrochlorothiazide in another group of 228 whites (P = 0.0018 and P = 0.00012). A different polymorphism (rs10739150) near PTPRD was associated with response to atenolol in 150 black hypertensive individuals (P = 8.25 × 10). rs12346562 had a similar trend in association with response to bisoprolol (a different β-blocker) in 207 Finnish men in the genetics of drug responsiveness in essential hypertension study. In addition, an intronic single-nucleotide polymorphism (rs4742610) in the PTPRD gene was associated with resistant hypertension in whites and Hispanics in the international verapamil SR trandolapril study (meta-analysis P = 3.2 × 10).PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.
- FIXED DOSE COMBINATIONS WITH SELECTIVE BETA-BLOCKERS: QUANTITATIVE DETERMINATION IN BIOLOGICAL FLUIDS. [Journal Article, Research Support, Non-U.S. Gov't]
- Rev Med Chir Soc Med Nat Iasi 2015 Apr-Jun; 119(2):585-91.
Hypertension is one of the most common causes of death, a complex and incompletely controlled disease for millions of patients. Metoprolol, bisoprolol, nebivolol and atenolol are selective beta-blockers frequently used in the management of arterial hypertension, alone or in fixed combination with other substances. This study presents the most used analytical methods for simultaneous determination in biological fluids of fixed combinations containing selective beta-blockers. Articles in Pub-Med, Science Direct and Wiley Journals databases published between years 2004-2014 were reviewed. Methods such as liquid chromatography--mass spectrometry--mass spectrometry (LC-MS/MS), high performance liquid chromatography (HPLC) or high performance liquid chromatography--mass spectrometry (HPLC-MS) were used for determination of fixed combination with beta-blockers in human plasma, rat plasma and human breast milk. LC-MS/MS method was used for simultaneous determination of fixed combinations of metoprolol with simvastatin, hydrochlorothiazide or ramipril, combinations of nebivolol and valsartan, or atenolol and amlodipine. Biological samples were processed by protein precipitation techniques or by liquid-liquid extraction. For the determination of fixed dose combinations of felodipine and metoprolol in rat plasma liquid chromatography--electrospray ionization--mass spectrometry (LC-ESI-MS/MS) was applied, using phenacetin as internal standard. HPLC-MS method was applied for the determination of bisoprolol and hydrochlorothiazide in human plasma. For the determination of atenolol and chlorthalidone from human breast milk and human plasma the HPLC method was used. The analytical methods were validated according to the specialized guidelines, and were applied to biological samples, thing that confirms the permanent concern of researchers in this field.
- Continuous Wavelet Transform, a powerful alternative to Derivative Spectrophotometry in analysis of binary and ternary mixtures: A comparative study. [Journal Article]
- Spectrochim Acta A Mol Biomol Spectrosc 2015 Dec 5.:945-55.
A comparative study was established between two signal processing techniques showing the theoretical algorithm for each method and making a comparison between them to indicate the advantages and limitations. The methods under study are Numerical Differentiation (ND) and Continuous Wavelet Transform (CWT). These methods were studied as spectrophotometric resolution tools for simultaneous analysis of binary and ternary mixtures. To present the comparison, the two methods were applied for the resolution of Bisoprolol (BIS) and Hydrochlorothiazide (HCT) in their binary mixture and for the analysis of Amlodipine (AML), Aliskiren (ALI) and Hydrochlorothiazide (HCT) as an example for ternary mixtures. By comparing the results in laboratory prepared mixtures, it was proven that CWT technique is more efficient and advantageous in analysis of mixtures with severe overlapped spectra than ND. The CWT was applied for quantitative determination of the drugs in their pharmaceutical formulations and validated according to the ICH guidelines where accuracy, precision, repeatability and robustness were found to be within the acceptable limit.
- Pharmacogenomics of hypertension: a genome‐wide, placebo‐controlled cross‐over study, using four classes of antihypertensive drugs. [Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- J Am Heart Assoc 2015 Jan; 4(1):e001521.
Identification of genetic markers of antihypertensive drug responses could assist in individualization of hypertension treatment.We conducted a genome-wide association study to identify gene loci influencing the responsiveness of 228 male patients to 4 classes of antihypertensive drugs. The Genetics of Drug Responsiveness in Essential Hypertension (GENRES) study is a double-blind, placebo-controlled cross-over study where each subject received amlodipine, bisoprolol,hydrochlorothiazide, and losartan, each as a monotherapy, in a randomized order. Replication analyses were performed in 4 studies with patients of European ancestry (PEAR Study, N=386; GERA I and II Studies, N=196 and N=198; SOPHIA Study, N=372). We identified 3 single-nucleotide polymorphisms within the ACY3 gene that showed associations with bisoprolol response reaching genome-wide significance (P<5x10(-8))however, this could not be replicated in the PEAR Study using atenolol. In addition, 39 single-nucleotide polymorphisms showed P values of 10(-5) to 10(-7). The 20 top-associated single-nucleotide polymorphisms were different for each antihypertensive drug. None of these top single-nucleotide polymorphisms co-localized with the panel of >40 genes identified in genome-wide association studies of hypertension. Replication analyses of GENRES results provided suggestive evidence for a missense variant (rs3814995) in the NPHS1 (nephrin) gene influencing losartan response, and for 2 variants influencing hydrochlorothiazide response, located within or close to the ALDH1A3 (rs3825926) and CLIC5 (rs321329) genes.These data provide some evidence for a link between biology of the glomerular protein nephrin and antihypertensive action of angiotensin receptor antagonists and encourage additional studies on aldehyde dehydrogenase–mediated reactions in antihypertensive drug action.
- Different signal processing techniques of ratio spectra for spectrophotometric resolution of binary mixture of bisoprolol and hydrochlorothiazide; a comparative study. [Comparative Study, Journal Article, Validation Studies]
- Spectrochim Acta A Mol Biomol Spectrosc 2015 Apr 5.:334-43.
Five signal processing techniques were applied to ratio spectra for quantitative determination of bisoprolol (BIS) and hydrochlorothiazide (HCT) in their binary mixture. The proposed techniques are Numerical Differentiation of Ratio Spectra (ND-RS), Savitsky-Golay of Ratio Spectra (SG-RS), Continuous Wavelet Transform of Ratio Spectra (CWT-RS), Mean Centering of Ratio Spectra (MC-RS) and Discrete Fourier Transform of Ratio Spectra (DFT-RS). The linearity of the proposed methods was investigated in the range of 2-40 and 1-22 μg/mL for BIS and HCT, respectively. The proposed methods were applied successfully for the determination of the drugs in laboratory prepared mixtures and in commercial pharmaceutical preparations and standard deviation was less than 1.5. The five signal processing techniques were compared to each other and validated according to the ICH guidelines and accuracy, precision, repeatability and robustness were found to be within the acceptable limit.
- Cyclodextrin Micellar LC for Direct Selective Analysis of Combined Dosage Drugs in Urine. [Evaluation Studies, Journal Article]
- J Chromatogr Sci 2015 Aug; 53(7):1123-30.
Two cyclodextrin micellar liquid chromatographic methods were developed and applied to the simultaneous determination of bisoprolol/hydrochlorothiazide and atenolol/chlorthalidone combinations in urine matrices without sample pretreatment. These combined β-blockers and diuretics chemotherapies are commonly used in the treatment of hypertension and cardiovascular diseases. Hybrid isocratic mobile phases containing hydroxypropyl-β-cyclodextrin, sodium dodecyl sulfate, phosphate buffer and methanol on a Luna C18 column with 0.5 mL min(-1) flow rate and 25.0°C column temperature were used. The methods were sensitive enough for the determination of analytes at the therapeutic urine levels with limits of detections down to 1.0 µg mL(-1); relative standard deviations and recoveries were ranged between 1.5-4.4% and 98.00-109.52%, respectively. Urinary excretion studies showed that the detection of drugs is possible up to 24 h after their ingestion. The selective proposed separations with less consumption of organic solvents over the hitherto ones could be attributed to the four point competitive interactions among analysts, pseudostationary phases and a real stationary phase.