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Sacubitril/valsartan, an angiotensin receptor‐neprilysin inhibitor, has demonstrated a superior blood pressure‐lowering effect compared with renin‐angiotensin system inhibitors in several clinical trials. However, there has been no available evidence on the comparison between sacubitril/valsartan and calcium channel blockers (CCBs), a well‐established class of antihypertensive drugs. In this open‐label, multicenter study, we aimed to demonstrate the efficacy and safety of sacubitril/valsartan versus amlodipine, one of the most widely used CCBs, after 8 weeks of treatment. A total of 359 Japanese patients with essential hypertension (office systolic blood pressure [SBP] ≥ 150 to < 180 mmHg), aged 18–79, were randomly assigned to receive either once‐daily sacubitril/valsartan 200 mg or once‐daily amlodipine 5 mg in a 1:1 allocation ratio. The primary endpoint was the noninferiority of sacubitril/valsartan compared with amlodipine in mean change in 24‐h SBP from baseline to Week 8, followed by a significance test as a secondary endpoint analysis. The mean change in 24‐h SBP in sacubitril/valsartan was noninferior to that in amlodipine (between‐treatment difference −0.62 mmHg [95% confidential interval: −3.23 to 1.98; p = 0.003 for noninferiority; independent t‐test with noninferiority margin 3.0 mmHg]), with no significant difference observed (p = 0.637). There was no significant difference in the incidence of adverse events (AEs). These results suggested that the blood pressure‐lowering effect of sacubitril/valsartan is comparable to that of amlodipine, with no marked differences in tolerability between the two groups. Sacubitril/valsartan, a potent antihypertensive drug comparable to amlodipine, is expected to improve blood pressure control in clinical practice.

The study aimed to investigate the pharmacokinetics and bioequivalence of coformulations of valsartan and amlodipine in healthy Chinese subjects under both fasting and fed conditions. The research was conducted under both fasting and fed studies and employed a single-center, randomized, open-label, single-dose, three-period design with partial-repeat and crossover elements. A total of 71 healthy Chinese adult participants were included under fasting (n = 36) and fed (n = 35) conditions. The subjects were orally administered valsartan/amlodipine tablets (80/5 mg) per cycle either as the test (T) or reference (R) formulation. The washout period was 14 days. Plasma concentrations of valsartan and amlodipine were determined using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the noncompartmental analysis method was used for estimating the pharmacokinetic parameters. Under fasting conditions, the within-subject standard deviations (S ) of maximum plasma concentration (C ), area under the concentration-time curve from time 0 to the time of the last-measurable plasma concentration (AUC ), and area under the concentration-time curve from time 0 extrapolated to infinity (AUC ) for valsartan were calculated to be ≥0.294 and evaluated by the reference-scaled average bioequivalence (RSABE) method. The point estimates of the geometric mean ratios (GMRs) of C , AUC and AUC for valsartan were 1.0805, 1.0991, and 1.1015 respectively, and the critical bounds were all less than 0. The S of C , AUC , and AUC for amlodipine were all <0.294, and the 90% confidence intervals (CIs) of the GMRs fell within the bioequivalence range, as evaluated by the average bioequivalence (ABE) method. Under the fed condition, the S of C , AUC , and AUC were all <0.294 for both valsartan and amlodipine; the ABE method was therefore employed for the evaluation of bioequivalence, and the 90% CIs of the GMRs fell within the bioequivalence range. All the observed adverse events were mild and transient. The two formulations of valsartan/amlodipine (80/5 mg) tablets were bioequivalent and safe.

•Ezetimibe (Eze)/atorvastatin (Ato) + amlodipine (Aml) is effective in lowering blood pressure and cholesterol over individual therapies.•Ezetimibe/Ato + Aml combination has a comparable safety profile to the Eze/Ato and Aml therapies.•The future development of Eze/Ato + Aml fixed-dose combination could enhance treatment adherence by lowering pill burden. This study aimed to evaluate the efficacy and safety of triple combination of ezetimibe (Eze)/atorvastatin (Ato) 10/40 mg + amlodipine (Aml) 10 mg therapy for lowering the low-density lipoprotein cholesterol (LDL-C) and blood pressure compared with either Eze/Ato 10/40 mg or Aml 10 mg therapies in patients with comorbid primary hypercholesterolemia and essential hypertension. This was a randomized, multicenter, double-blind, active-controlled, Phase III clinical trial. Participants underwent a wash-out period (2 weeks for nonfibrate medications, 6 weeks for fibrates) followed by 4 weeks of therapeutic lifestyle changes. Subsequently, 109 participants were randomly assigned to 3 groups: (1) Eze/Ato 10/40 mg + Aml 10 mg, (2) Eze/Ato 10/40 mg, and (3) Aml 10 mg. The coprimary end points were percentage change in LDL-C and change in mean sitting systolic blood pressure (SBP) compared with baseline at week 8. A total of 109 participants were enrolled in the study, and there were no statistically significant differences in the baseline characteristics of participants across the 3 groups. After 8 weeks of treatment, the least-square (LS) mean (SE) of percent change from baseline in LDL-C was −57.95% (3.52%) for the Eze/Ato 10/40 mg + Aml 10 mg group and 8.93% (3.54%) for the Aml 10 mg group. The LS mean difference (SE) between these 2 groups was statistically significant at −66.88 (4.95) (95% CI, −76.77% to −56.99%) (P < 0.0001). Furthermore, at week 8, the LS mean (SE) change in mean sitting SBP between the Eze/Ato 10/40 mg + Aml 10 mg group and the Eze/Ato 10/40 mg group was −19.24 (2.42) mm Hg and −4.43 (2.56) mm Hg, respectively. The LS mean difference (SE) between the 2 groups was statistically significant −14.81 (3.53) (95% CI, −21.87 to −7.74) mm Hg (P < 0.0001). No serious adverse drug reactions occurred in any of the study groups. Triple combination therapy with Eze/Ato + Aml has effectively reduced the LDL-C and SBP independently, compared with either Eze/Ato or Aml therapies over 8 weeks of treatment period. In terms of safety, there were no significant differences among the 3 treatment groups. This research lays the groundwork for the development of a triple fixed-dose combination in the future, which could improve patient convenience and adherence by reducing pill burden. Clinical Research Information Service (CRIS), Republic of Korea: KCT0006283.

Effective antihypertensive therapy is essential for achieving optimal blood pressure (BP) control and reducing cardiovascular events. This double-blind, multicenter, randomized trial aimed to compare the antihypertensive efficacy and safety of a combination of amlodipine (AML) and candesartan cilexetil (CC) versus AML monotherapy in patients with essential hypertension (HTN). After a 4-week run-in period with AML 5 mg, patients whose HTN remained uncontrolled (diastolic BP [DBP]) ≥ 90 mmHg and < 120 mmHg) were randomized to receive either AML + CC or AML alone for 8 weeks. Efficacy was assessed by measuring changes in DBP and systolic BP (SBP). The primary safety measure was the incidence of adverse events (AEs). A total of 174 participants were included in the efficacy analysis. After 8 weeks, DBP decreased by -9.92 ± 0.86 mmHg in the AML + CC arm and - 2.08 ± 0.86 mmHg in the AML arm ( p  < 0.0001). SBP decreased by -14.27 ± 1.39 mmHg in the AML + CC arm versus - 2.77 ± 1.39 mmHg in the AML arm ( p  < 0.0001). AEs occurred in 11.24% of the AML + CC group and 5.62% of the AML group ( p  = 0.1773). AML + CC combination therapy demonstrated superior efficacy with good tolerance, making it a promising option for patients with inadequately controlled hypertension on amlodipine alone.

This study aimed to compare systolic blood pressure (SBP) time in target range (TTR), long‐term blood pressure (BP) variability (BPV), and BP control across age groups (18–45, 46–64, 65–79, ≥80 years) in patients with primary hypertension treated with amlodipine‐based antihypertensive therapy for ≥12 months. Data were obtained from adult patients enrolled in the China Hypertension Center who received amlodipine‐based antihypertensive therapy. Demographics, BP measurements, and laboratory results were recorded. Baseline characteristics, SBP TTR, long‐term BPV, and BP control were compared among age groups. A total of 36 153 patients were included: 2681 in the 18–45 group, 14 300 in the 46–64 group, 15 595 in the 65–79 group, and 3577 in the ≥ 80 group. Younger and middle‐aged patients demonstrated better indicator improvements. SBP TTR declined with age (82.52% ± 19.68%, 81.98% ± 20.69%, 79.10% ± 22.96%, and 78.33% ± 23.50%, respectively; p < 0.001). BP control also declined with age (84.04%, 83.20%, 80.44%, and 79.59%, respectively; p < 0.001). BPV increased with age, though not significantly (p = 0.051). During follow‐up, SBP TTR and BP control improved, while BPV declined, with most changes reaching statistical significance. Across all age groups, SBP TTR remained above 78% throughout follow‐up. Long‐term continuous use of amlodipine is beneficial for achieving improved BP control, enhanced TTR, and reduced BPV.

Aim of the Study: To investigate the primary monomer components and the associated mechanisms of action of DOC in exerting antihypertensive effects with Western medicine. Materials and Methods: In this study, UPLC-Q-TOF/MS technology was used to analyze the blood components of DOC and its interaction with Western medicine. The antihypertensive effects of serum monomer components were also evaluated. Blood pressure measurements for experimental animals were recorded before administration, at three hours and twenty-four hours after the first administration, as well as the same time of the last administration of the treatment cycle. Meanwhile, the antihypertensive mechanism was explored through the integration of network pharmacology and molecular docking technology. Results: Blood component analyses revealed the identification of five compounds in the serum: Kaempferide, Rutin, Syringaldehyde, Paeoniflorin, and Hyperoside. In terms of serum drug concentrations, Irbesartan and Amlodipine concentrations were multiplied by 1.36 and 0.56, respectively, following the combination therapy of Chinese and Western medicine compared with the Western medicine alone group. The concentrations of Paeoniflorin, Kaempferin, and Syringaldehyde in the combination group were significantly higher than those observed in the DOC group. The results from pharmacodynamic experiments indicated that the antihypertensive effect achieved through the combined application of Chinese and Western medicine on SHRs was superior to that resulting from the dual administration of two types of Western medicines alone. Conclusion: The combination of DOC with two Western medications has been shown to significantly enhance antihypertensive effects in SHRs. Furthermore, five major monomers present in the serum of experimental rats post-treatment exhibit notable antihypertensive properties. Keywords: spontaneously hypertensive, seropharmacology, network pharmacology, Dendrobium officinale, Paeonia lactiflora

We investigated the effects of age, sex, BMI, total number of prescribed daily pills, common biomarkers, and CYP3A4/5 polymorphisms on dose‐adjusted amlodipine concentration (CDR) in hypertensive patients. We also examined associations between the same covariates, dose, and serum amlodipine concentrations with uncontrolled hypertension. Amlodipine concentrations were measured in 471 patients treated with ≥ 2 antihypertensive drugs, with 50% having uncontrolled hypertension (daytime ambulatory blood pressure ≥ 135 mmHg). CYP analyses were performed in a subgroup of 258 patients, 82% of these uncontrolled. Women used lower daily doses (p < 0.001) and had higher CDR (p < 0.001) than men. CDR increased with age (p < 0.001), reduced kidney function (p < 0.001) and CYP3A4*22 allele (p = 0.006). Patients with uncontrolled hypertension had lower CDR (p = 0.014). Women were half as likely as men to have uncontrolled hypertension (p = 0.002). At the group level, a 20 nmol/L increase in concentration, corresponding to adjustment from 5 to 10 mg, was associated with a 16.5% decreased probability of uncontrolled hypertension. Female sex, increasing age, reduced kidney function, and reduced CYP3A4 activity increased amlodipine CDR. The included covariates explained 41% of the amlodipine concentration variability. Females had a reduced probability of uncontrolled hypertension, and increased amlodipine concentration was associated with decreased probability of uncontrolled hypertension. We suggest using TDM of amlodipine as an aid for clinical decision‐making in cases of unsatisfactory treatment response, to identify possible non‐adherence or pharmacokinetic deviations. Trial Registration: ClinicalTrials.gov identifier: NCT03209154 Forest plot of the multivariate logistic regression model evaluating odds for uncontrolled hypertension, defined as day‐time systolic ambulatory blood pressure ≥ 135 mmHg in 455 patients with treated hypertension.

This study aimed to assess the efficacy and safety of a combination therapy of Allisartan Isoproxil 240 mg and Amlodipine 5 mg (ALI/AML) compared to AML 5 mg monotherapy in patients with mild‐to‐moderate essential hypertension. In this phase III, multicenter, double‐blind, parallel‐group, randomized controlled trial, patients aged 18–70 years with mean sitting systolic blood pressure (msSBP) between 140 and <180 mmHg and mean sitting diastolic blood pressure (msDBP) between 90 and <110 mmHg, following a 4‐week treatment with AML 5 mg, were randomized 1:1 to receive either ALI/AML or AML once daily for 12 weeks. This 12‐week double‐blind period was followed by an open‐label extension of ALI/AML treatment through week 52. A total of 300 patients were enrolled, with 149 and 151 patients randomly assigned to ALI/AML and AML groups, respectively. Of these, 257 patients completed the study. Baseline demographics and characteristics were comparable between groups. After 12 weeks, the reduction in msSBP (the primary endpoint) was significantly greater in the ALI/AML group compared to the AML group (–15.7 vs. –10.2 mmHg, p = 0.0019). Similarly, reductions in msDBP (–5.7 vs. –2.4 mmHg, p < 0.001) and 24‐h mean ambulatory SBP and DBP (–10.4 and –7.7 mmHg vs. –5.6 and –3.8 mmHg) were more pronounced in the ALI/AML group. Additionally, a higher proportion of patients achieved both a BP response and target office BP in the ALI/AML group compared to the AML group (51.4% vs. 37.4%, 42.5% vs. 30.6%, both p < 0.05). The ALI/AML combination was generally well tolerated, and the antihypertensive effect was maintained for up to 52 weeks. In patients with essential hypertension inadequately controlled by AML, the ALI/AML combination provided superior reductions in msSBP and was significantly more effective than AML monotherapy. This once‐daily single‐pill combination demonstrated promising efficacy and tolerability. Trial Registration: ClinicalTrials.gov identifier: NCT06465264

There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients’ and physicians’ satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug‐related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM‐AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

The incidence of hypertension in persons 25 years of age and older is estimated to be 46% in Africa, where it is still very common. This concerning rate could be explained by the pharmaceutical markets' accessibility to poor quality antihypertensive drugs. Thus, the purpose of this study was to evaluate and compare the quality different brands of Amlodipine Tablets Commercially available in Jimma Town, South-western Ethiopia. The quality control test was conducted from August 30, 2019 to February 27, 2020 at Jimma University in the Laboratory of Drug Quality Control (JuLaDQ). The laboratory test was carried out in accordance with WHO inspection guidelines and United States Pharmacopeia. A statistically significant was considered when P<0.05. For further comparison of the in-vitro dissolution profiles of amlodipine tablets, model-independent model-dependent parameters and statistical Dunnetts tests for ensuring bioequivalence were used to further compare the in-vitro dissolution profiles. With the exception of brand AMD-5 (1/10), the remaining nine (n = 9) brands were within WHO visual inspection criteria. The quality control parameters such as friability, weight variation, identity, assay, and dissolution test were within the United States Pharmacopeia. The model independent parameters (f1, and f2) confirmed that, all generic products were bio-equivalence, and interchangeable with comparator product. The model dependent approaches revealed the Weibull model (AMD-10), the Zero order (AMD-3), and the Korsemeyer-Peppas models were the most effective predictions for the release of the pharmaceutical substance from the dosage form. The Korsemeyer-Peppas model (r2 ≥0.9695) was the best descriptive model for determining the amlodipine drug kinetics from the point of view of all brands examined. The evaluated amlodipine brand tablets were in line with quality standards. The model independent methods confirmed that the generic brand tablets were interchangeable in clinical practice. The tested products follow more than two drug release kinetics. The study revealed a manifest discrepancy in the dissolution profiles' releases. Therefore, it is strongly advised to use appropriately designed dissolution profile evaluation methods with various pH values in the dissolution media, as well as to do comprehensive visual inspections. This will make it easier to do a thorough investigation of any potential quality issues that might be related to various generic products available in the pharmaceutical market.