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El objetivo de este artículo es comparar las propiedades químicas y farmacológicas del telmisartán y el losartán, y su metabolito activo EXP3174, con el fin de entender por qué el telmisartán es efectivo en pacientes hospitalizados con Covid-19 mientras que el losartán no lo es. Se llevó a cabo una revisión bibliográfica exhaustiva de las propiedades químicas, farmacocinéticas y farmacodinámicas de ambos fármacos y se destacaron las diferencias más importantes que podrían estar relacionadas con su efectividad en pacientes con Covid-19. Se concluyó que las propiedades farmacológicas del telmisartán, como su mayor afinidad por el receptor AT1, su duración de acción prolongada y su capacidad para modular la inflamación podrían explicar su efectividad en pacientes con Covid-19. Por otro lado, las propiedades farmacológicas del losartán, como su menor afinidad por el receptor AT1 y su rápido metabolismo, pueden limitar su efectividad en pacientes con Covid-19. Estos resultados resaltan la importancia de comprender las propiedades químicas y farmacológicas de los medicamentos para identificar posibles candidatos terapéuticos efectivos en el tratamiento de Covid-19. (AU)
The objective of this article is to compare the chemical and pharmacological properties of telmisartan and losartan and their active metabolite EXP3174 to understand why telmisartan is effective in hospitalized patients with COVID-19 while losartan is not. A comprehensive literature review of the chemical, pharmacokinetic and pharmacodynamic properties of both drugs was done to highlight the most important differences that may be related to their efficacy in patients with COVID-19. It was concluded that the pharmacological properties of telmisartan, such as its higher affinity for the AT1 receptor, its long duration of action and its ability to modulate inflammation, could explain its efficacy in patients with COVID-19. On the other hand, the pharmacological properties of losartan, such as its lower affinity for the AT1 receptor and its rapid metabolism, may limit its efficacy in patients with COVID-19. These results highlight the importance of understanding the chemical and pharmacological properties of drugs to identify potential effective therapeutic candidates for the treatment of COVID-19. (AU)
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Losartan/pharmacology , Telmisartan/pharmacology , COVID-19 Drug Treatment , Controlled Clinical Trials as Topic , Losartan/chemistry , Angiotensin II Type 1 Receptor Blockers/pharmacology , Telmisartan/chemistry , HospitalizationABSTRACT
Background: Hypertension is a chronic disease and is a major risk factor for chronic heart disease, stroke, coronary heart disease, and its complications include heart failure, peripheral vascular disease, renal impairment, retinal hemorrhage, and visual impairment. Antihypertensive drugs are important to avoid such complications but compliance of patient is needed which may depend on the cost of therapy. Aim and Objective: This study aimed to assess the efficacy and safety of a branded generic with an economical generic. Materials and Methods: Out of 110 patients, 105 patients (53 patients in group A and 52 patients in group B) completed the study with follow-up over a period of 6 months. Group A patients received generic Telmisartan 40 mg in the beginning (0th day) which was continued for 12 weeks, cross-over was done with branded generic Telmisartan (Telma 40) which was given for further 3 months. Group B patients received the branded generic followed by generic Telmisartan in that sequence for 3 months each. Blood pressure (BP) was recorded at the baseline visit and at the end of 4, 8, 12, 16, 20, and 24 weeks. The adverse events were assessed throughout the study period. Results: Intra-group comparison show significant reduction in systolic (SBP) and diastolic BP (DBP) in each groups (P < 0.001) but when we compare the reduction of SBP and DBP in between the two groups the difference was not significant. Common adverse events were headache, dizziness, light-headedness, and vertigo. Conclusion: There was a huge difference between the prices of branded generic and unbranded generic. This study showed that both branded generic and unbranded generic are comparable in terms of efficacy, safety except the cost of therapy. Thus substitution of a Pharmacological generic (unbranded generic) drug could save lot of expenses.
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Background: In hypertensive patients with impaired fasting glycaemia (IFG), the incidence of Type 2 diabetes mellitus is 20%, which further worsens the situation. Currently, no approved drug is available for the treatment of IFG. Telmisartan has partial agonistic activity at the PPAR? receptor, thereby reducing insulin resistance. Hence, this study was undertaken. Aim and Objectives: Primary objective: To evaluate the effect of telmisartan on glycosylated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels. Secondary objective: To evaluate the effect of telmisartan on Body Mass Index (BMI). Materials and Methods: In this prospective observational study, 100 newly diagnosed cases of hypertension with IFG were included. Before the treatment with telmisartan, baseline parameters such as Glycosylated haemoglobin (HbA1c), FPG, BMI, and blood pressure (BP) were recorded. Then, follow-up was done at 4, 8, and 12 weeks. BP and FPG were repeated at 4 and 8 weeks, whereas at 12 weeks all the four parameters were repeated. All the study endpoints were analyzed using paired t-test. Results: In this study, telmisartan reduced mean HbA1c from 5.87 ± 0.09 to 5.66 ± 0.17%, FPG levels from 111.49 ± 3.82 to 104.28 ± 4.60 mg/dl, BMI from 24.20 ± 1.84 to 23.80 ± 1.75 kg/m2 and SBP from 148.44 ± 3.64 to 133.43 ± 3.00, DBP from 91.90 ± 2.37 to 82.08 ± 2.45 mm of Hg at the end of 12 weeks of treatment (P < 0.001). There were no serious adverse effects observed during the study period. Conclusion: In this study, telmisartan reduced HbA1c, FPG, BMI, and BP values significantly. Hence, telmisartan is safe and has a significant effect on the reduction of both BP and insulin resistance.
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@#Objective To investigate the effects of telmisartan on the proliferation, migration and apoptosis of non-small cell lung cancer A549 and the mechanism of regulating Wnt signaling pathway. Methods Non-small cell lung cancer cell line A549 was cultured in vitro. Cell counting kit-8 (CCK-8) assay was used to detect the effect of telmisartan at different concentrations on the proliferative activity of A549 cells. The survival fraction of A549 treated with different concentrations of telmisartan was determined by colony-formation assay. The effect of telmisartan at different concentrations on the migration ability of A549 cells was examined in the wounding healing assay. Hoechst staining was used to detect the effects of telmisartan at different concentrations on the apoptosis of A549. Western bloting was used to detect the expressions of β-actin, proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, Wnt-3a, Beta-catenin (β-catenin), serine protein kinase 3β (p-GSK-3β), glycogen synthase kinase-3β (GSK-3β) and c-myc. Results Different concentrations of telmisartan treatment inhibited the proliferation activity, colony-formation rate and migration of A549 cells, and reduced the expression of PCNA in a concentration-dependent manner. Telmisartan treatment promoted the apoptosis of A549 cells, significantly increased the expression of pro-apoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2. The expression levels of Wnt-3a, β-catenin, p-GSK-3β, and c-myc in A549 cells increased after treatment with telmisartan, while the expression levels of GSK-3β decreased. Conclusion Telmisartan may play a role in the proliferation, migration and apoptosis of non-small cell lung cancer A549 cells, and inhibiting the Wnt/β-catenin signaling pathway may be one of the mechanisms.
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RESUMEN INTRODUCCIÓN: El parkinsonismo es un síndrome clínico, caracterizado por temblor, rigidez y bradicinesia, debido a la alteración en el circuito dopaminérgico ganglio-basal, específicamente a nivel nigroestriatal. A continuación se presenta un caso de parkinsonismo inducido por telmisartán. PRESENTACIÓN DE CASO: Hombre de 78 años, con antecedentes de enfermedad de Parkinson de dos años de evolución, controlada con levodopa, pramipexol ER y amantadina, ingresa al servicio de urgencias por empeoramiento del parkinsonismo en las dos semanas previas a la consulta. Tenía antecedente de infarto cerebral en el territorio de la arteria cerebral posterior izquierda, hipertensión arterial crónica y diabetes mellitus tipo 2. Al examen neurológico presentaba bradicinesia y rigidez severa en las cuatro extremidades, con limitación significativa de la marcha, asociado a mioclonías. Se descartaron alteraciones infecciosas, metabólicas y lesiones agudas en la tomografía cerebral, por lo que se suspendió el telmisartán, posteriormente a lo cual los síntomas mejoraron. DISCUSIÓN: El parkinsonismo secundario a fármacos constituye la primera causa de este síndrome, en varios modelos farmacológicos se describe la acción que estos ejercen sobre los receptores dopaminérgicos. Así, el parkinsonismo inducido por telmisartán se considera desencadenado por disrupción dopaminérgica secundaria al antagonismo de los receptores de la angiotensina II a nivel de la sustancia gris periacueductal.
SUMMARY INTRODUCTION: Parkinsonism is a clinical syndrome characterized by tremor, rigidity, and bradykinesia due to alteration in the basal-ganglia dopaminergic circuit, specifically at the nigrostriatal level. The following is a case of parkinsonism induced by telmisartan. CASE PRESENTATION: A 78-year-old man with a 2-year history of Parkinson's disease of controlled evolution with levodopa, pramipexole ER, amantadine was admitted to the emergency department due to worsening of parkinsonism in the two weeks prior to consultation. He had a history of cerebral infarction in the territory of the left posterior cerebral artery, chronic arterial hypertension, and type 2 diabetes mellitus. On neurological examination, he presented bradykinesia and severe stiffness in all four limbs with significant limitation of gait, associated with myoclonus. Infectious and metabolic alterations and acute lesions were ruled out in the brain tomography, so telmisartan was suspended, after which the symptoms improved. DISCUSSION: Drug-induced parkinsonism is the first cause of this syndrome, and the action they exert on dopaminergic receptors has been described in several pharmacological models. Telmisartan-induced parkinsonism is considered triggered by dopaminergic disruption secondary to angiotensin II receptor antagonism at the periaqueductal gray substance level.
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Transit-Oriented DevelopmentABSTRACT
Current work discloses the sensitive LC-MS/MS method development for the trace level determination of genotoxicimpurity 2-Methyl-6-nitro aniline in Telmisartan. 2-Methyl-6-nitro aniline was determined by LC-MS/MS methodin selected ion monitoring mode using LiChrospher RP-18 (100 × 4.6 mm) 5.0 µm column. Gradient technique wasapplied for the elution of analytes using acetonitrile (mobile phase A) and 0.01 M ammonium acetate buffer (mobilephase B) in different ratios. The gradient program (T/%B) was set as 0/5, 2.50/15, 5.00/30, 10.00/50, 15.00/95, and20.00/95. Developed method was validated as per International Conference on Harmonization guidelines. The limit ofdetection and limit of quantitation values found for 2-Methyl-6-nitro aniline were 0.05 and 0.1 µg/ml. The developedmethod serves as an upright tool in quality control for quantitation of 2-Methyl-6-nitro aniline impurity at trace levelsin Telmisartan.
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Background: Depression and hypertension are common morbidities which are seen in elderly and also one leads to the other. Present antidepressant drugs are known for its side effects and there is a necessary for newer drugs with lesser adverse effects. Telmisartan being a widely used antihypertensive drug and with multiple additional properties like peroxisome proliferator-activated receptor gamma activity along with blunting of renin-angiotensin-aldosterone system can be a potential drug for depression. Hence this study is aimed to evaluate the antidepressant activity of angiotensin receptor blocker telmisartan in animal models.Methods: As per protocol submitted to ethics committee, 24 male albino mice weighing between 20-30grams of either sex were selected and divided into 4 groups consisting of 6 each. They were housed in cages with food and water ad libitum. Animals were kept in ambient temperature and humidity, with a 12-hour light and 12-hour dark cycle. Group 1 and group 2 were administered distilled water and fluoxetine 10 mg/kg respectively only on day 15, whereas group 3 and group 4 received telmisartan per orally 1 mg/kg and 2 mg/kg respectively for 15 days once daily. All animals were tested on day 15 using tail suspension test for antidepressant effect.Results: There was significant reduction in the immobility time in telmisartan group when compared to the control group and this time was comparable with the immobility time of standard drug fluoxetine. Decrease in immobility time was found to statistically significant by using one-way ANOVA followed by Bonferroni post hoc test.Conclusions: As evident from our study, telmisartan can be a newer target for antidepressant effect.
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Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are being used as first line agents for the treatment of hypertension in haemodialysis patients as well as in the general population. Serious hyperkalemia is common in patients with end-stage renal disease, and is observed in about 10% of haemodialysis patients. Although many research have been done so far to compare the antihypertensive efficacy of ARBs, but such studies to evaluate the effect on serum urea, creatinine and potassium levels are not so common in North India region.Methods: In this open label, prospective, randomized study, we evaluated the effect on serum urea, creatinine and potassium levels with use of ARB’s (olmesartan or telmisartan) in stage 1 hypertensive patients (JNCVII). 60 patients were randomized in to two groups. The odd numbers will be allotted olmesartan 20 mg (group A) and even numbers to telmisartan 40 mg (group B). Impacts on serum urea, creatinine and potassium levels were evaluated after 12 weeks.Results: Our results indicates that there was no statistically significant alterations in mean serum creatinine, blood urea and in mean serum potassium levels compared to baseline within the two groups as well as when mean of both groups were compared, olmesartan showed a better reduction in blood pressure as compared to telmisartan.Conclusions: Olmesartan showed a better reduction in blood pressure with similar effects in biochemical parameters as telmisartan.
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Background: Hypertension management is of paramount importance in diabetic patients for reduction of cardiovascular and other complications. The objective of the present study was to assess prescribing pattern of antihypertensive drugs in hypertensive type 2 diabetic patients and evaluate them by comparing with Eighth Joint National Committee (JNC-8) hypertension treatment guidelines.Methods: A prospective observational study was carried out on 110 hypertensive type 2 diabetic patients of age 41-80 years visiting outpatient department of Medicine at G.S. Medical College and Hospital, UP, India for 4 months. JNC-8 hypertension management guideline was considered while evaluating the prescribed drugs. All the relevant data was collected from the prescription card of the patient on a preformed performa and analyzed using descriptive statistics.Results: Total of 176 drugs was prescribed to the study patients among which two drug combination therapy (55.45%) was mostly used. The most common group prescribed was angiotensin receptor blocker (ARB) (29.45%) and ARB+CCB (calcium channel blockers) (34.92%) were the commonest fixed drug combination. Overall, it was amlodipine (21.47%) that was most frequently prescribed among all antihypertensive drugs.Conclusions: ARB was the most commonest class, ARB+CCB was the most frequent fixed drug combination prescribed to the study patient while amlodipine was the highly utilized individual antihypertensive drug in the study. Prescriptions evaluation revealed that 94.88% prescription were rational and were in accordance with the JNC-8 hypertension treatment guidelines except the use of beta blockers (5.12%).
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Background: Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II Receptor Blockers (ARBs) have become keystones of therapy for hypertension but there are very few studies where they have been compared with each other. This study attempted to compare the effect of Ramipril and Telmisartan on Blood Pressure and Insulin Resistance in Hypertensive patients (JNC 8).Methods: An open label, randomized, prospective and comparative study of twelve- week duration was conducted on 60 patients of hypertension (JNC-8), with the collaboration of Department of Pharmacology and Department of Medicine, Government Medical College, Amritsar. Group A and B were given Telmisartan 40mg and Ramipril 2.5 mg OD respectively. Blood Pressure was recorded on every visit, whereas, fasting plasma insulin and HOMA-IR values were recorded at the baseline and at the end of the study. Fasting blood sugar was done at 0, 4 and 12 weeks.Results: At the end of 12 weeks, a significant reduction in Systolic/Diastolic blood pressure was observed in group A with a drop of ~14/9 mmHg (p<0.001) and in group B too, the fall of ~11.6/7.2 mmHg was significant (p<0.001). However, in inter-group comparison only SBP difference was significant between two groups (p<0.05). Change in HOMA-IR value was also significant in both the groups (p<0.001). The inter-group difference for HOMA-IR between both the groups (A vs B) was also statistically significant (p<0.01).Conclusions: Telmisartan 40 mg OD was more effective than Ramipril 2.5 mg OD in controlling the SBP and improving Insulin resistance at the end of 12 weeks.
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BACKGROUND: Apart from its blood pressure-lowering effect by blocking the renin-angiotensin-aldosterone system, telmisartan, an angiotensin II type 1 receptor blocker (ARB), exhibits various ancillary effects including cardiovascular protective effects in vitro. Nonetheless, the protective effects of telmisartan in cerebrocardiovascular diseases are somewhat variable in large-scale clinical trials. Dysregulation of endothelial nitric oxide (NO) synthase (eNOS)-derived NO contributes to the developments of various vascular diseases. Nevertheless, the direct effects of telmisartan on endothelial functions including NO production and vessel relaxation, and its action mechanism have not been fully elucidated. Here, we investigated the mechanism by which telmisartan regulates NO production and vessel relaxation in vitro and in vivo. METHODS: We measured nitrite levels in culture medium and mouse serum, and performed inhibitor studies and western blot analyses using bovine aortic endothelial cells (BAECs) and a hyperglycemic mouse model. To assess vessel reactivity, we performed acetylcholine (ACh)-induced vessel relaxation assay on isolated rat aortas. RESULTS: Telmisartan decreased NO production in normoglycemic and hyperglycemic BAECs, which was accompanied by reduced phosphorylation of eNOS at Ser¹¹⁷⁹ (p-eNOS-Ser¹¹⁷⁹). Telmisartan increased the expression of protein phosphatase 2A catalytic subunit (PP2Ac) and co-treatment with okadaic acid completely restored telmisartan-inhibited NO production and p-eNOS-Ser¹¹⁷⁹ levels. Of the ARBs tested (including losartan and fimasartan), only telmisartan decreased NO production and p-eNOS-Ser¹¹⁷⁹ levels, and enhanced PP2Ac expression. Co-treatment with GW9662 had no effect on telmisartan-induced changes. In line with in vitro observations, telmisartan reduced serum nitrite and p-eNOS-Ser¹¹⁷⁹ levels, and increased PP2Ac expression in high fat diet-fed mice. Furthermore, telmisartan attenuated ACh-induced rat aorta relaxation. CONCLUSION: We demonstrated that telmisartan inhibited NO production and vessel relaxation at least in part by PP2A-mediated eNOS-Ser¹¹⁷⁹ dephosphorylation in a peroxisome proliferator-activated receptor γ-independent manner. These results may provide a mechanism that explains the inconsistent cerebrocardiovascular protective effects of telmisartan.
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Animals , Mice , Rats , Acetylcholine , Aorta , Blotting, Western , Catalytic Domain , Endothelial Cells , In Vitro Techniques , Losartan , Mice, Obese , Nitric Oxide Synthase Type III , Nitric Oxide , Okadaic Acid , Peroxisomes , Phosphorylation , Protein Phosphatase 2 , Receptor, Angiotensin, Type 1 , Relaxation , Renin-Angiotensin System , Vascular DiseasesABSTRACT
OBJECTIVE@#To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction.@*METHODS@#Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting.@*RESULTS@#The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin.@*CONCLUSIONS@#Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
Subject(s)
Animals , Male , Mice , Angiotensin II Type 1 Receptor Blockers , Antihypertensive Agents , Extracellular Matrix Proteins , Metabolism , Fibrosis , Kidney , Metabolism , Pathology , Membrane Proteins , Genetics , Metabolism , Mice, Inbred C57BL , RNA, Small Interfering , Random Allocation , Telmisartan , Pharmacology , Transforming Growth Factor beta1 , Pharmacology , Ureteral Obstruction , MetabolismABSTRACT
OBJECTIVE:To investigate the long-term economic consequences of candesartan cilexetilirbesartan and telmisartan in preventing stroke and myocardial infarction (MI) among hypertension patients using Markov model, to offer the reference for hypertension intervention. METHODS:A Markov state transition model was built based on the natural history of hypertension from the societal perspective to estimate the expected health care costs and the quality adjusted life years. Meanwhile, the incremental cost-effectiveness ratio was obtained. One year cycle length and 20 years horizon were adopted. The 5% yearly discount rate was applied to both health care costs and QALYs. One-way sensitivity analysis, second-order Monte-Carlo and probabilistic sensitivity analysis were performed. RESULTS:Candesartan cilexetil was at an absolute disadvantage because of the highest cost and the lowest effect in the baseline analysis. The incremental cost-effectiveness ratio for irbesartan versus telmisartan was 5 799.67 yuan/QALY. The sensitivity analysis was consistent with the baseline results. CONCLUSION:Irbesartan shows significant economic advantage at the threshold of 49 992 yuan/QALY compared with telmisartan. And candesartan cilexetil is with less economical.
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BACKGROUND: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice.METHODS: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase α (G6Pase-α), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ζ (PKCζ) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice.RESULTS: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a 40 μM concentration without a change in G6Pase-α expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 (p-IRS-1-Ser302) and decreased p-IRS-1-Tyr632 dose-dependently. Telmisartan dose-dependently increased p-PKCζ-Thr410 which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative PKCζ significantly attenuated telmisartan-induced HGP and p-IRS-1-Ser302 and -inhibited p-IRS-1-Tyr632. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased p-IRS-1-Ser302 and decreased p-IRS-1-Tyr632, which was accompanied by an increase in p-PKCζ-Thr410.CONCLUSION: These results suggest that telmisartan increases HGP by inducing p-PKCζ-Thr410 that increases p-IRS-1-Ser302 and decreases p-IRS-1-Tyr632 in a PPARγ-independent manner.
Subject(s)
Animals , Mice , Blotting, Western , Diabetes Mellitus, Type 2 , Diet, High-Fat , Ectopic Gene Expression , Glucose , Glucose-6-Phosphatase , Hep G2 Cells , Insulin Receptor Substrate Proteins , Insulin , Liver , Losartan , Peroxisomes , Phosphoenolpyruvate , Phosphorylation , Protein Kinase C , Protein Kinases , Receptor, Angiotensin, Type 1 , Receptor, Insulin , SerineABSTRACT
Objective To investigate the clinical efficacy and mechanism of rosuvastatin combined with telmisartan in the treatment of persistent atrial fibrillation. Methods One hundred and twenty patients with persistent atrial fibrillation admitted to Cangzhou Central Hospital from February 2015 to February 2018 were enrolled and they were divided into study group and control group by random envelope method, with 60 patients in each group. The patients in study group were treated with rosuvastatin combined with telmisartan; and in control group they were treated with telmisartan, and after treatment for 6 weeks the clinical efficacy was observed. Resting heart rates were observed in two groups. The left atrial inner diameter, left atrium left and right diameter, left atrial sphericity index and left ventricular end diastolic volume, left ventricular end systolic volume, left ventricular posterior wall thickness of two groups were detected by ultrasond before and after treatment; the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were tested by enzyme linked immunosorbent assay (ELISA) in two groups before and after treatment; and the level of serum hypersensitive C-reactive protein (hs-CRP) was detected by immunoturbidimetry;the level of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was tested by immunoluminometric assay. Results Resting heart rate was significantly decreased in study group after treatment compared with that before treatment (bpm: 76.37±7.25 vs. 89.76±8.79, P < 0.05), while in control group, the comparison of resting heart rate before and after treatment was of no statistical significant differences (bpm: 90.71±8.56 vs. 87.80±6.26, P > 0.05), resulting that the post-treatment resting heart rate of study group was significantly lower than that of control group (bpm:76.37±7.25 vs. 87.80±6.26, P < 0.05). After treatment, the left atrial inner diameter, left atrium left and right diameter, left atrial sphericity index and left ventricular end diastolic volume were increased compared with those before treatment in both groups; after treatment, above various index levels in study group were lower than those of control group [left atrial inner diameter (mm): 40.68±3.86 vs. 41.99±3.97, left atrium left and right diameter (mm): 41.07±2.85 vs. 42.69±2.90, left atrial sphericity index: 0.77±0.08 vs. 0.86±0.07, left ventricular end diastolic volume (mL): 107.48±32.90 vs. 118.98±35.75, all P < 0.05]. There were no statistical significant differences between the two groups in left ventricular end systolic volume and posterior wall thickness of left ventricle after treatment [study group: left ventricular end systolic volume (mL) was 38.59±12.37 vs. 39.81±12.03, posterior wall thickness of left ventricle (mm) was 11.34±2.39 vs. 12.80±3.27, control group: left ventricular end systolic volume (mL) was 39.90±11.54 vs. 40.65±11.50, posterior wall thickness of left ventricle (mm) was 11.90±2.57 vs. 12.99±3.16, all P > 0.05]. Besides, the serum levels of TNF-α, IL-6 and hs-CRP were obviously decreased in two groups after treatment (all P < 0.05), after treatment, above indexes in study group were significantly lower than those in control group [TNF-α (ng/L): 29.76±5.31 vs. 36.63±5.11, IL-6 (ng/L): 14.37±3.36 vs. 22.65±4.58, hs-CRP (mg/L): 13.68±2.75 vs. 20.63±2.69, all P < 0.05]. Plasma NT-proBNP was increased in control group after treatment compared with that before treatment (μg/L: 431.80±42.54 vs. 365.89±39.81, P < 0.05), whereas there was no significant difference in the study group between pre- and post-treatment (μg/L: 351.80±38.76 vs. 346.89±35.82, P > 0.05), resulting in post-treatment plasma NT-proBNP significantly lower in study group (P < 0.05). Conclusions Rosuvastatin combined with telmisartan can prevent left atrial remodeling in patients with persistent atrial fibrillation and delay the dysfunction of left ventricular pump. The therapeutic mechanism was related to the decrease in the levels of serum inflammatory factors in patients treated with such therapy.
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Background: Cardiovascular disease (CVD) is the most common contributor of morbidity and mortality in underdeveloped and developing countries including the South Asian countries (including India and Pakistan). Amongst the cluster group of CVDs, Hypertension (HTN) represents the most common cardiovascular risk factor. The aim of this trial was to evaluate of antihypertensive efficacy and effect on biochemical parameters of Losartan + Hydrochlorthiazide versus Telmisartan + Hydrochlorthiazide in patients with stage 1 or stage 2 hypertension with a randomized controlled trial.Methods: This was a prospective, randomized controlled trial of Losartan + Hydrochlorthiazide versus Telmisartan + Hydrochlorthiazide in patients with stage 1 or stage 2 hypertension. The primary endpoint on treatment was analysis of antihypertensive efficacy of these drug combinations. The variables were compared at different time points- baseline, 3 and 6 months.Results: In the present study, 76 patients were enrolled with 38 patients each allocated to each treatment groups. The effect of Losartan 50mg + Hydrochlorthiazide 12.5mg OD was found to be significant on SBP and DBP in both supine as well as sitting position than Telmisartan 80mg + Hydrochlorthiazide 12.5mg OD group at 3 and 6 months.Conclusions: The results on anti- hypertensive efficacy was far better in Losartan 50mg + Hydrochlorthiazide 12.5mg OD group than Telmisartan 80mg + Hydrochlorthiazide 12.5mg OD group.
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Background: Objectives of the study was to study the effect of Azilsartan 40mg once daily versus Telmisartan 40mg once daily in patients with Grade I-II essential hypertension.Methods: A prospective study was conducted at MGM Medical college and Hospital which included 80 patients in each group with Grade I–II essential hypertension. The sex, age, presenting illness, and family history of the patients were recorded. Investigations such as blood sugar, urine analysis, kidney function test, lipid profile, and ECG were performed before starting the treatment. Any adverse effects during the treatment were noted. Blood pressure was recorded at baseline and during follow-up. One group received Azilsartan 40mg once daily and another group Telmisartan 40mg once daily. Patients were followed-up every week for 5 weeks.Results: Patients receiving Azilsartan 40mg and Telmisartan 40mg showed a significant fall (P <0.05) in systolic (SBP) at the end of fifth week, when compared to baseline and diastolic blood pressure (DBP) significant fall at fourth and fifth week. The difference in fall in SBP and DBP was insignificant between the groups, after first, second and third week (P >0.05). Adverse effects such as Nasopharyngitis, Upper respiratory tract inflammation, Gastroenteritis, headache, dizziness, and fatigue were reported with both drugs.Conclusions: Reduction of blood pressure with Azilsartan and Telmisartan was similar, but fall in blood pressure from baseline was highly significant in both groups.
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OBJECTIVE: To explore the similarity of the dissolution curves of self-made and original telmisartan /hydrochlorothiazide tablets and provide basis for the prescription and process screening of self-made preparation and the quality similarity evaluation with original preparation. METHODS: The dissolution curves of telmisartan and hydrochlorothiazide from self-made and original preparations in four different dissolution media were determined using HPLC. The HPLC method was performed on Welch Ultimate XB-C8 column (4.6 mm × 250 mm, 5 μm) with mobile phase A consisting of ammonium dihydrogen phosphate solution (2.0 g ammonium dihydrogen phosphate was dissolved in 1 L water then adjusted to pH 3.0 with phosphoric acid) and mobile phase B consisting of acetonitrile- methanol (50:50) at a flow rate of 1.2 mL•min-1. The detection wavelength was set at 270 nm. The injection volume was 20 μL. Then f2 factor method was used to evaluate the similarity. RESULTS: The dissolution curves of self-made and original preparations of telmisartan /hydrochlorothiazide tablets in different dissolution media showed similarity, with the f2 factor ≥50 or the dissolution rate within 15 min≥85%. CONCLUSION: The dissolution behaviors of self-made and original telmisartan /hydrochlorothiazide tablets are basically similar, which indicates that the prescription and technology of self-made preparation are reasonable and feasible.
ABSTRACT
It was recently reported that the C(max) and AUC of rosuvastatin increases when it is coadministered with telmisartan and cyclosporine. Rosuvastatin is known to be a substrate of OATP1B1, OATP1B3, NTCP, and BCRP transporters. The aim of this study was to explore the mechanism of the interactions between rosuvastatin and two perpetrators, telmisartan and cyclosporine. Published (cyclosporine) or newly developed (telmisartan) PBPK models were used to this end. The rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect racial differences in rosuvastatin exposure. In the telmisartan–rosuvastatin case, simulated rosuvastatin C(maxI)/C(max) and AUC(I)/AUC (with/without telmisartan) ratios were 1.92 and 1.14, respectively, and the T(max) changed from 3.35 h to 1.40 h with coadministration of telmisartan, which were consistent with the aforementioned report (C(maxI)/C(max): 2.01, AUCI/AUC:1.18, T(max): 5 h → 0.75 h). In the next case of cyclosporine–rosuvastatin, the simulated rosuvastatin C(maxI)/C(max) and AUC(I)/AUC (with/without cyclosporine) ratios were 3.29 and 1.30, respectively. The decrease in the CL(int,BCRP,intestine) of rosuvastatin by telmisartan and cyclosporine in the PBPK model was pivotal to reproducing this finding in Simcyp. Our PBPK model demonstrated that the major causes of increase in rosuvastatin exposure are mediated by intestinal BCRP (rosuvastatin–telmisartan interaction) or by both of BCRP and OATP1B1/3 (rosuvastatin–cyclosporine interaction).
Subject(s)
Area Under Curve , Cyclosporine , Drug Interactions , Rosuvastatin CalciumABSTRACT
OBJECTIVE: To study the effects of telmisartan combined with finasteride on blood pressure rhythm (BPR) in non-dipper type hypertension patients with benign prostatic hyperplasia (BPH). METHODS: From Jul. 2015 to Dec. 2016, medical information of 190 patients with non-dipper type hypertension complicated with BPH were retrospectively collected from Halison International Peace Hospital, and then divided into control group (n=82) and observation group (n=108) according to therapy plan. Control group was given telmisartan 40 mg, qd; observation group was additionally given finasteride 5 mg, qd, on the basis of observation group. Both groups were treated for 12 months, and followed up once every 3 months. The changes of blood pressure (24 hSBP, 24 hDBP, 24 hPP, dSBP, dDBP, dPP, nSBP, nDBP, nPP), morning blood pressure surge, prostate volume, nocturia times, the changes of BPR (the rate of non-dipper type blood pressure change) were observed in 2 groups. The occurrence of ADR was observed. RESULTS: Before treatment, there was no statistical significance in blood pressure, morning blood pressure surge, prostate volume or nocturia times between 2 groups (P>0. 05). After treated for 3, 6, 12 months, blood pressure, morning blood pressure surge, prostate volume, nocturia times and the rate of non-dipper type blood pressure change in 2 groups were decreased significantly; the observation group was significantly lower than the control group, with statistical significance (P>0. 05). There was no statistical significance in the incidence of ADR between 2 groups (P>0. 05). CONCLUSIONS: Telmisartan combined with finasteride show significant effects on non-dipper hypertension complicated with BPH, effectively reduce the level of blood pressure, prostate volume, nocturia times and improve BPR with good safety. The effect of two-drug is better than that of telmisartan.