In a trial involving patients with recurrent kidney stones who received once-daily 12.5-mg, 25-mg, or 50-mg doses of hydrochlorothiazide or placebo, the incidence of stone recurrence was similar in ...all groups.
Hypertension affects an estimated 88 million Americans and is controlled to the recommended blood pressure (BP) goal of <140/90 mmHg in only 37% of individuals with hypertension. The benefits of ...achieving these goals, including significant reductions in cardiovascular morbidity and mortality, are well documented. Thus, a concerted effort to improve BP goal attainment is required. The majority of patients will require two or more antihypertensives to achieve BP goal. It has been shown that administering two drugs in a single-dose formulation substantially improves patient compliance compared with separate agent administration.
Fixed-dose combination therapy can offer potential advantages over individual agents, including increased efficacy, reduced incidence of adverse effects, lower healthcare costs, and improved patient compliance through the use of a single medication administered once daily. Currently available fixed-dose agents include several combinations with complementary pharmacodynamic activity.
This article reviews the fixed-dose antihypertensive combinations currently available in the US, and assesses the published literature comparing fixed-dose combinations with co-administration of two separate drugs or with other combinations. An analysis of the published literature between 1987 and 2007 reveals that most studies of fixed-dose antihypertensive combinations have compared the combination with monotherapy (53%); many fewer published papers have compared a fixed combination with coadministration of similar drugs as separate agents (2%), a fixed combination with another fixed combination from the same class (7%), or with a combination of agents from a different class (9%). Other comparisons have been with placebo, baseline or between generic formulations. This analysis indicates that: (i) physicians can be assured that a fixed-dose combination is more effective than either agent given as monotherapy; (ii) there is a paucity of data comparing different fixed-dose combinations; and (iii) very few studies have investigated the impact of fixed-dose combinations on achievement of BP goals, including both systolic BP and diastolic BP. For clinical decision making, physicians should rely on how the agents perform when administered together in add-on studies and how each component performs as monotherapy in reducing BP, achieving BP goals and reducing outcomes, as well as considering patient factors such as response to and tolerance of such agents as monotherapy and cost.
The availability of effective and well tolerated fixed-dose combination antihypertensive agents should encourage primary-care physicians to be more willing to use such therapies in a timely manner when BP goals are not being achieved with monotherapy. This approach would improve BP control rates in the US and worldwide.
The occurrence of fifty-five pharmaceuticals, hormones and metabolites in raw waters used for drinking water production and their removal through a drinking water treatment were studied. Thirty-five ...out of fifty-five drugs were detected in the raw water at the facility intake with concentrations up to 1200 ng/L. The behavior of the compounds was studied at each step: prechlorination, coagulation, sand filtration, ozonation, granular activated carbon filtration and post-chlorination; showing that the complete treatment accounted for the complete removal of all the compounds detected in raw waters except for five of them. Phenytoin, atenolol and hydrochlorothiazide were the three pharmaceuticals most frequently found in finished waters at concentrations about 10 ng/L. Sotalol and carbamazepine epoxide were found in less than a half of the samples at lower concentrations, above 2 ng/L. However despite their persistence, the removals of these five pharmaceuticals were higher than 95%.
► Thirty-five out of fifty-five drugs detected in raw waters. ► Drinking treatment effectively removes 30 out of 35 target pharmaceuticals. ► Phenytoin, atenolol, sotalol, hydrochlorothiazide and carbamazepine epoxide detected in finished waters.
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The development of poorly water-soluble drugs faces the risk of low bioavailability and therapeutic efficacy. The co-amorphous drug delivery system has recently gained considerable ...interest because it offers an alternative approach to modify properties of poorly water-soluble drugs. Herein, we developed a co-amorphous system of atenolol (ATE) and poorly water-soluble hydrochlorothiazide (HCT) by means of cryogenic milling. The co-administration of ATE and HCT has been reported to show therapeutic advantages for patients with uncomplicated hypertension. The co-amorphous ATE-HCT sample with 1:1 molar ratio showed excellent physical stability, which could be attributed to the formation of strong molecular interactions between ATE and HCT as evidenced by FT-IR spectra. Compared to the pure crystalline form, amorphous form and physical mixture, HCT in the co-amorphous form exhibited the significantly increased intrinsic dissolution rate, as well as the enhanced bioavailability in the pharmacokinetic study. It was found that the enhanced bioavailability of HCT in the co-amorphous formulation was achieved by the synergistic effect of amorphized HCT and the water-soluble coformer ATE. The present study provides an improved approach to implement the combination therapy of ATE and HCT for potential clinical treatments.
The hydrochlorothiazide (HCT) low solubility and permeability give rise to limited and variable bioavailability; its low stability makes it difficult to develop stable aqueous liquid formulations; ...its low dose makes the achievement of a homogeneous drug distribution very difficult. Thus, the aim of this study was to investigate the effectiveness of a strategy based on the development of nanostructured lipid carriers (NLC) as an innovative oral pediatric formulation of HCT with improved therapeutic efficacy. The performance of various synthetic and natural liquid lipids was examined and two different preparation methods were employed, i.e. homogenization-ultrasonication (HU) and microemulsion (ME), in order to evaluate their influence on the NLC properties in terms of size, polydispersity index, ζ-potential, entrapment efficiency, gastric stability, and drug release properties. Precirol®ATO5 was used as solid lipid and Tween
®
80 and Pluronic
®
F68 as surfactants, formerly selected in a previous study focused on the development of HCT-solid lipid nanoparticles (SLNs). The presence of Pluronic
®
F68 did not allow ME formation. On the contrary, using Tween
®
80, the ME method enabled a higher entrapment efficiency than the HU. Regardless of the preparation method, NLCs exhibited great entrapment efficiency values clearly higher than previous SLNs. Moreover, NLC-ME formulations provided a prolonged release, which lasted for 6 h. In particular, NLC-ME containing Tween
®
20 as Co-Surfactant showed the best performances, giving rise to a complete drug release, never achieved with previous SLN formulations, despite their successful results. In vivo studies on rats confirmed these results, displaying their best diuretic profile. Moreover, all HCT-loaded NLC formulations showed higher stability than the corresponding SLNs.
Aims
Sodium–glucose co‐transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing ...renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic‐like physiologic effects, we compared dapagliflozin and hydrochlorothiazide (HCTZ) effects on 24‐h blood pressure (BP), body weight, plasma volume and glomerular filtration rate (GFR).
Methods
In this randomized, placebo‐controlled, double‐blind trial, 75 subjects with type 2 diabetes were assigned placebo, dapagliflozin 10 mg/day, or HCTZ 25 mg/day. Changes from baseline BP, body weight, plasma volume and GFR were assessed after 12 weeks of treatment.
Results
Subjects' mean age was 56 years, type 2 diabetes mellitus (T2DM) duration 6.3 years, and haemoglobin A1c (HbA1c) 7.5%. Treatment with placebo, dapagliflozin or HCTZ resulted in changes from baseline in 24‐h ambulatory mean systolic blood pressure (SBP) of −0.9 (95%CI −4.2, +2.4), −3.3 (95%CI −6.8, +0.2), and −6.6 (95%CI −9.9, −3.2) mmHg, respectively at week 12, adjusted for baseline SBP. Body weight decreased with dapagliflozin and HCTZ. In a sub‐study plasma volume appeared to decrease with dapagliflozin but did not change with placebo or HCTZ treatment. Dapagliflozin induced a greater reduction in GFR (−10.8%; 95%CI −14.6, −6.7) relative to placebo (−2.9%; 95% CI −6.9, +1.2) or HCTZ (−3.4%; 95%CI −7.3, +0.6).
Conclusions
Dapagliflozin‐induced SGLT2 inhibition for 12 weeks is associated with reductions in 24‐h BP, body weight, GFR and possibly plasma volume. Cumulatively, these effects suggest that dapagliflozin may have a diuretic‐like capacity to lower BP in addition to beneficial effects on glycaemic control.
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