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British Journal of Clinical Pharmacology Jun 19821 The blood pressure lowering effect of xipamide, a non-thiazide diuretic given for 6 weeks was compared in a randomised cross-over trial with that of cyclopenthiazide... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1 The blood pressure lowering effect of xipamide, a non-thiazide diuretic given for 6 weeks was compared in a randomised cross-over trial with that of cyclopenthiazide in 14 patients with essential hypertension. 2 Xipamide 10 or 20 mg given once daily was as effective in lowering supine blood pressure as daily cyclopenthiazide 0.5 mg. There was no difference in the blood pressure lowering effect of 10 mg xipamide daily for 2 weeks compared to 20 mg daily given for a further 4 weeks. 3 Plasma potassium was reduced by both drugs, but markedly more after both 10 mg and 20 mg xipamide than after cyclopenthiazide 0.5 mg. By the sixth week of treatment 13 of 14 patients on xipamide but only 6 of 14 on cyclopenthiazide has plasma potassium concentrations of, or less than, 3.5 mmol/l. The fall in plasma potassium was significantly greater and the final plasma potassium concentration was significantly lower after either dose of xipamide than after cyclopenthiazide. 4 These results suggest that 10 mg or 20 mg of xipamide daily is effective in lowering blood pressure in hypertensive patients but is associated with hypokalaemia. In view of recent evidence linking diuretic-induced hypokalaemia with cardiac dysrhythmias in patients with essential hypertension we would suggest that thiazide diuretics be used in preference to xipamide for the routine management of essential hypertension. Our results also suggest that the currently recommended dose of xipamide (20 mg) for the treatment of hypertension is excessive, and lower amounts than 10 mg per day might possibly be as effective in lowering blood pressure with less adverse metabolic consequences.
Topics: Adult; Blood Glucose; Blood Pressure; Cyclopenthiazide; Diuretics; Female; Humans; Hypertension; Male; Middle Aged; Potassium; Renin; Sodium Chloride Symporter Inhibitors; Time Factors; Xipamide
PubMed: 7046777
DOI: 10.1111/j.1365-2125.1982.tb01879.x -
BMC Chemistry Sep 2022A new rapid, simple, and sensitive RP-HPLC method was carried out through applying Quality by Design approach for determination of xipamide and valsartan in Human...
A new rapid, simple, and sensitive RP-HPLC method was carried out through applying Quality by Design approach for determination of xipamide and valsartan in Human plasma. Fractional factorial design was used for screening of four independent factors: pH, flow rate, detection wavelength, and % of MeOH. Analysis of variance (ANOVA) confirmed that flow rate and % of MeOH were only significant. Chromatographic conditions optimization was carried out through using central composite design. Method analysis was performed using BDS Hypersil C8 column (250 × 4.6 mm, 5 μm) and an isocratic mobile phase of MeOH and 0.05 M KHPO buffer pH 3 (64.5:35.5, v/v) at 1.2 mL/min flow rate with UV detection at 240 nm and 10 μL injection volume. According to FDA guidelines, the method was then validated for the determination of the two drugs clinically in human plasma in respect of future pharmacokinetic and bioequivalence simulation studies. The standard curve was linear in the concentration range of 5-100 µg/mL for both drugs, with a determination coefficient (R) of 0.999. Also, the average recoveries lied within the range from 99.89 to 100.03%. The proposed method showed good predictability and robustness.
PubMed: 36127740
DOI: 10.1186/s13065-022-00864-4 -
BMC Chemistry May 2023Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The...
Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The purpose of this research is the quantitative and qualitative analysis of this binary mixture by green univariate and multivariate spectrophotometric methods. Univariate methods were zero order absorption spectra method (D) and Fourier self-deconvolution (FSD), as TRI was directly determined by D at 367.0 nm in the range (2.00-10.00 µg/mL), where XIP show no interference. While XIP was determined by FSD at 261.0 nm in the range (2.00-8.00 µg/mL), where TRI show zero crossing. Multivariate methods were Partial Least Squares, Principal Component Regression, Artificial Neural Networks, and Multivariate Curve Resolution-Alternating Least Squares. A training set of 25 mixtures with different quantities of the tested components was used to construct and evaluate them, 3 latent variables were displayed using an experimental design. A set of 18 synthetic mixtures with concentrations ranging from (3.00-7.00 µg/mL) for TRI and (2.00-6.00 µg/mL) for XIP, were used to construct the calibration models. A collection of seven synthetic mixtures with various quantities was applied to build the validation models. All the proposed approaches quantitative analyses were evaluated using recoveries as a percentage, root mean square error of prediction, and standard error of prediction. Strong multivariate statistical tools were presented by these models, and they were used to analyze the combined dosage form available on the Egyptian market. The proposed techniques were evaluated in accordance with ICH recommendations, where they are capable of overcoming challenges including spectral overlaps and collinearity. When the suggested approaches and the published one were statistically compared, there was no discernible difference between them. The green analytical method index and eco-scale tools were applied for assessment of the established models greenness. The suggested techniques can be used in product testing laboratories for standard pharmaceutical analysis of the substances being studied.
PubMed: 37179391
DOI: 10.1186/s13065-023-00956-9 -
British Medical Journal (Clinical... Mar 1982
Topics: Aged; Diuretics; Female; Humans; Hypokalemia; Indapamide; Male; Xipamide
PubMed: 6802373
DOI: No ID Found -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2016A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene...
A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L(-1) orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min(-1) flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195-100 μg mL(-1) for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.
Topics: Calibration; Chromatography, High Pressure Liquid; Hydrochlorothiazide; Powders; Reproducibility of Results; Triamterene; Xipamide
PubMed: 26959547
DOI: 10.1515/acph-2016-0022 -
Journal of Pharmaceutical Analysis Feb 2020Acetazolamide (molecular mass (MM), 222) belongs to the class of sulfonamides (R-SO-NH) and is one of the strongest pharmacological inhibitors of carbonic anhydrase...
GC-NICI-MS analysis of acetazolamide and other sulfonamide (R-SO-NH) drugs as pentafluorobenzyl derivatives [R-SO-N(PFB)] and quantification of pharmacological acetazolamide in human urine.
Acetazolamide (molecular mass (MM), 222) belongs to the class of sulfonamides (R-SO-NH) and is one of the strongest pharmacological inhibitors of carbonic anhydrase activity. Acetazolamide is excreted unchanged in the urine. Here, we report on the development, validation and biomedical application of a stable-isotope dilution GC-MS method for the reliable quantitative determination of acetazolamide in human urine. The method is based on evaporation to dryness of 50 μL urine aliquots, base-catalyzed derivatization of acetazolamide (d-AZM) and its internal standard [-H]acetazolamide (d-AZM) in 30 vol% pentafluorobenzyl (PFB) bromide in acetonitrile (60 min, 30 °C), reconstitution in toluene (200 μL) and injection of 1-μL aliquots. The negative-ion chemical ionization (NICI) mass spectra (methane) of the PFB derivatives contained several intense ions including [M] at 581 for d-AZM and 584 for d-AZM, suggesting derivatization of their sulfonamide groups to form -dipentafluorobenzyl derivatives (R-SO-N(PFB)), i.e., d-AZM-(PFB) and d-AZM-(PFB), respectively. Quantification was performed by selected-ion monitoring of 581 and 83 for d-AZM-(PFB) and 584 and 86 for d-AZM-(PFB). The limits of detection and quantitation of the method were determined to be 300 fmol (67 pg) and 1 μM of acetazolamide, respectively. Intra- and inter-assay precision and accuracy for acetazolamide in human urine samples in pharmacologically relevant concentration ranges were determined to be 0.3%-4.2% and 95.3%-109%, respectively. The method was applied to measure urinary acetazolamide excretion after ingestion of a 250 mg acetazolamide-containing tablet (Acemit®) by a healthy volunteer. Among other tested sulfonamide drugs, methazolamide (MM, 236) was also found to form a -dipentafluorobenzyl derivative, whereas dorzolamide (MM, 324) was hardly detectable. No GC-MS peaks were obtained from the PFB bromide derivatization of hydrochlorothiazide (MM, 298), xipamide (MM, 355), indapamide and metholazone (MM, 366 each) or brinzolamide (MM, 384). We demonstrate for the first time that sulfonamide drugs can be derivatized with PFB bromide and quantitated by GC-MS. Sulfonamides with MM larger than 236 are likely to be derivatized by PFB bromide but to lack thermal stability.
PubMed: 32123599
DOI: 10.1016/j.jpha.2019.11.006 -
British Journal of Pharmacology Jan 2014Loop diuretics are widely used to inhibit the Na(+), K(+), 2Cl(-) co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR)...
BACKGROUND AND PURPOSE
Loop diuretics are widely used to inhibit the Na(+), K(+), 2Cl(-) co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Here, we investigated the mechanism of CFTR inhibition by loop diuretics and explored the effects of chemical structure on channel blockade.
EXPERIMENTAL APPROACH
Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR.
KEY RESULTS
When added to the intracellular solution, loop diuretics inhibited CFTR Cl(-) currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to loop diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl(-) channels with 'very fast' speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with 'intermediate' speed and drug-induced blocking events were distinct from channel closures.
CONCLUSIONS AND IMPLICATIONS
Structure-activity analysis of the loop diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking loop diuretics within the intracellular vestibule of the CFTR pore. We conclude that loop diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity.
Topics: Animals; Bumetanide; Chlorides; Cricetinae; Cystic Fibrosis Transmembrane Conductance Regulator; Dose-Response Relationship, Drug; Furosemide; Humans; Kinetics; Membrane Potentials; Mice; Molecular Structure; Rats; Sodium Potassium Chloride Symporter Inhibitors; Structure-Activity Relationship; Sulfonamides; Xipamide
PubMed: 24117047
DOI: 10.1111/bph.12458 -
British Medical Journal (Clinical... May 1982
Topics: Adult; Aged; Diuretics; Humans; Indapamide; Middle Aged; Potassium; Ventricular Fibrillation
PubMed: 6804002
DOI: 10.1136/bmj.284.6326.1407 -
British Journal of Clinical Pharmacology Sep 19811 The antihypertensive activity of the diuretic xipamide has been studied in 18 patients with mild/moderate essential hypertension using the technique of continuous...
1 The antihypertensive activity of the diuretic xipamide has been studied in 18 patients with mild/moderate essential hypertension using the technique of continuous ambulatory intra-arterial blood pressure recording. Full data from 48 h blood pressure recordings before and after treatment were available from 13 patients. 2 After a mean period of 3 months' treatment with xipamide 20 mg once daily, both systolic and diastolic blood pressure were markedly reduced throughout the whole 24 h day, the reductions of systolic being statistically significant throughout the whole period, and of diastolic for 19 out of the 24 hourly periods measured. There was no postural hypotension seen during treatment and there was a conspicuous lack of side effects. 3 Xipamide would appear to be as effective as many beta-adrenoceptor blockers but without their side effects and produces a better control of blood pressure throughout the whole day and night.
Topics: Ambulatory Care; Antihypertensive Agents; Blood Pressure; Circadian Rhythm; Diuretics; Drug Evaluation; Humans; Hypertension; Monitoring, Physiologic; Xipamide
PubMed: 7295468
DOI: 10.1111/j.1365-2125.1981.tb01230.x -
British Journal of Clinical Pharmacology Oct 1984In patients with uncontrolled hypertension addition of xipamide 20 mg daily to bendrofluazide 5 mg daily produced no significant additive antihypertensive effect, and... (Comparative Study)
Comparative Study
In patients with uncontrolled hypertension addition of xipamide 20 mg daily to bendrofluazide 5 mg daily produced no significant additive antihypertensive effect, and the 95% confidence limits excluded a clinically important response. Xipamide treatment worsened hypokalaemia and increased the blood urea concentration significantly.
Topics: Bendroflumethiazide; Blood Pressure; Diuretics; Drug Synergism; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Random Allocation; Xipamide
PubMed: 6487502
DOI: 10.1111/j.1365-2125.1984.tb02514.x