Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telmisartan (Micardis (R)) is a new, orally active, long-acting angio-tensin (Ang) II receptor antagonist that is effective in the treatment of hypertension. Ambulatory blood pressure monitoring (ABPM) has emerged as an important method for evaluating the consistency of the antihypertensive effects of a drug throughout the dosing interval. ABPM was used to evaluate the antihypertensive efficacy of telmisartan in several placebo-controlled, double-blind, multicenter studies. Patients with mild-to-moderate hypertension were allocated randomly to groups to receive telmisartan 40 or 80 mg, losartan 50 mg, or placebo, once daily in a 6-week, fixed-dose study, or telmisartan 40-120 mg, amlodipine 5-10 mg, or placebo, once daily in a 12-week, dose-titration study. Patients treated with telmisartan 40 and 80 mg or placebo in a separate 4-week, fixed-dose study were included in an additional analysis. Telmisartan 40 and 80 mg significantly decreased mean ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) relative to placebo for the entire 24 h period and in the following intervals: day (6 a.m. to 10 p.m.), morning (6 a.m. to noon), night (10 p.m. to 6 a.m), and the last 4 h of the dosing interval (P<0.01). Notably, telmisartan 40 or 80 mg was more effective than losartan, especially during the last 4-6 h of the dosing interval (P<0.05). Telmisartan 40- 120 mg tended to be more effective than amlodipine 5-10 mg in reducing SBP and DBP in each time interval, with significant differences between treatments noted for DBP in the last 4 h of the dosing interval and in the morning (P < 0.05). ABPM also revealed that the magnitude of the blood pressure decreasing effect with telmisartan was consistent throughout the dosing interval. These results demonstrate that telmisartan maintains a normal circadian blood pressure pattern and provides full 24 h blood pressure control with once-daily dosing.
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PMID:Use of ambulatory blood pressure monitoring to evaluate the selective angiotensin II receptor antagonist, telmisartan, and other antihypertensive drugs. 1090 41

Telmisartan (Micardis) is a potent, long-lasting, nonpeptide angiotensin II type-1 (AT(1)) receptor blocker (ARB) that is indicated for the treatment of essential hypertension. In receptor binding studies, telmisartan showed a high affinity and selectivity for the human AT(1) receptors compared with AT(2) receptors and a slower dissociation rate from the human AT(1) receptor than those of ARBs. In isolated aorta rings, telmisartan was shown to be an insurmountable antagonist of AII-induced contractions. The inhibitory effects of telmisartan on AII-induced contraction persisted even after wash-out procedures. In animal models such as spontaneous hypertension rats and renovascular hypertensive rats, telmisartan produced the consistent reduction of blood pressure. Furthermore, there were no rebound phenomenon and no tolerance to the drug developed in the repeated oral administration. Telmisartan has a longer terminal elimination half-life (about 24 h) than the other ARBs. In patients with mild-moderate hypertension, trough/peak ratios for telmisartan were above 80%. In Japanese patients with mild-moderate hypertension, telmisartan produced a significant reduction in blood pressure (effective rate: 76.0%) with a good safety profile. Therefore, telmisartan is expected to be effective in the treatment of hypertension, producing sustained 24-h blood pressure control.
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PMID:[Pharmacological and clinical profile of telmisartan, a selective angiotensin II type-1 receptor blocker]. 1522 20

Effects of Micardis (Telmisartan), alone or with low-dose aspirin, on blood pressure and other cardiovascular endpoints are examined in 20 patients with MESOR-hypertension in a crossover, double-blind, randomized study consisting of three stages, each lasting 7 days: I-placebo, II-Micardis, and III-Micardis with low-dose aspirin. Treatment was administered each day at a different circadian stage, upon awakening, and 3, 6, 9, 12, 15 and 18 hr after awakening. During each stage, the following variables were measured at 3-hr intervals during waking: systolic and diastolic blood pressure, heart rate, ejection fraction, intrarenal resistive index, acceleration time, and serum creatinine. Each data series was analyzed by single cosinor. Results were summarized by population-mean least squares spectra. At matched treatment times, the MESOR and circadian amplitude of each variable were compared among the three treatments by paired t-tests. A prominent circadian rhythm characterizes all variables. Micardis was associated not only with a lowering of blood pressure, but also with a reduction of the circadian blood pressure amplitude. The ejection fraction was increased, and the resistive index and acceleration time were decreased, the effect being more pronounced when low-dose aspirin was added to Micardis. Any circadian-stage dependent effect of Micardis, with or without low-dose aspirin, will require monitoring over spans longer than a single day for a given treatment administration time.
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PMID:Chronobiologically explored effects of Telmisartan. 1583 74

There is a growing body of evidence that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Indeed, large clinical trials have demonstrated a substantial benefit of the blockade of this system for cardiovascular-organ protection. Although several types of angiotensin II type 1 (AT1) receptor blockers (ARBs) are commercially available for the treatment of patients with hypertension, comparisons of the binding affinity to AT1 receptor among them remain to be elucidated. In this study, we examined the dissociation rate of several ARBs from AT1 receptor in vitro. Angiotensin II time-dependently dissociated telmisartan, olmesartan, candesartan, valsartan, losartan and an active metabolite of losartan, EXP3174, from membrane components containing human AT1 receptor The dissociation rate constant of each ARB was 0.003248, 0.004171, 0.005203, 0.009946, 0.01027 and 0.008561 min(-1), with corresponding half-lives of 213, 166, 133, 70, 67 and 81 min, respectively. These results demonstrate that telmisartan has the strongest binding affinity to AT1 receptor among various ARBs examined herein. The rank order of affinity was telmisartan > olmesartan > candesartan > EXP3174 > or = valsartan > or = losartan. The present findings suggest that telmisartan (Micardis) may have long-lasting blood pressure-lowering effects and superior cardioprotective properties in patients with hypertension due to its strongest AT1 receptor antagonistic ability.
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PMID:Telmisartan has the strongest binding affinity to angiotensin II type 1 receptor: comparison with other angiotensin II type 1 receptor blockers. 1586 75

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.
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PMID:Telmisartan: a review of its use in the management of hypertension. 1639 68

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. There is widespread agreement that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of insulin resistance and cardiovascular disease in diabetes. Indeed, large clinical trials have demonstrated substantial benefit of the blockade of this system for cardiovascular end-organ protection. Thus the blockade of the RAS may be a promising strategy for the treatment of the patients with the metabolic syndrome. Although several types of angiotensin II type 1 (AT(1)) receptor blockers (ARBs) are commercially available for the treatment of patients with hypertension, we have recently found that telmisartan (Micardis) could have the strongest binding affinity to AT(1) receptor. Further, telmisartan is reported to act as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These observations suggest that, due to its unique PPAR-gamma-modulating activity, telmisartan may be one of the most promising sartans for the treatment of cardiometabolic disorders. In this paper, we reviewed the potential utility of telmisartan in insulin resistance and vascular complications in diabetes.
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PMID:Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating activity for the treatment of cardiometabolic disorders. 1769 61

There is a growing body of evidence that the renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Indeed, large clinical trials have demonstrated substantial benefit of the blockade of this system for cardiovascular-organ protection. Although several types of angiotensin II type 1 (AT(1)) receptor blockers (ARBs) are commercially available for the treatment of patients with hypertension, we have recently found that telmisartan (Micardis) could have the strongest binding affinity to AT(1) receptor. Telmisartan will be a promising cardiometabolic sartan due to its unique peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-inducing properties as well. In this review, we focused on telmisartan, and discussed its potential therapeutic implications in cardiometabolic disorders.
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PMID:Telmisartan, its potential therapeutic implications in cardiometabolic disorders. 1822 Oct 77

Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus, Micardis HCT, PritorPlus] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management of patients with hypertension.
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PMID:Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension. 1872 41

Telmisartan (TLM), a nonpeptide angiotensin II antagonist, is widely prescribed for treating arterial hypertension and marketed by the innovator with the trade name of Micardis and Micardis plus. Telmisartan exhibits low aqueous solubility in the pH range of 3-7, which is the physiological pH. For addressing the issue of poor solubility of TLM, its commercial form makes use of inorganic alkalinizers. The present work illustrates the attempt to improve the solubility of telmisartan via a crystal engineering approach. A novel solid form of telmisartan with phthalic acid was obtained through the solution crystallization method (TPS) and the reaction crystallization method (TPR). Both the forms (TPS and TPR) were thoroughly characterized by powder diffraction X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and 1H NMR and were identified to be two different crystalline forms. Solubility studies of TPS and TPR were conducted at varying pH of phosphate buffer, and they exhibited 11-fold and 22-fold increased solubility, respectively, when compared to that of the pure drug at pH 5, which is within the pH of small intestine at which telmisartan is best absorbed orally from the systemic circulation.
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PMID:Enhanced Solubility of Telmisartan Phthalic Acid Cocrystals within the pH Range of a Systemic Absorption Site. 3145 96