Abstract:
:Candesartan cilexetil is rapidly and completely hydrolysed to the active compound candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, long-acting, selective angiotensin II AT1 receptor blocker. The pharmacokinetics of candesartan were investigated after single and repeated once-daily doses of candesartan cilexetil in the dose range 2-16 mg in both younger (19-40 years) and elderly (65-78 years) healthy volunteers in five studies. Blood pressure, heart rate, and hormones associated with the renin-angiotensin system, and safety of candesartan cilexetil administration were also assessed. Placebo comparisons were made in four studies. Frequent blood samples were collected after the first single dose of candesartan cilexetil, and during the last dosing interval after 1 week repeated once-daily administration. Serum and plasma were analysed for candesartan cilexetil, candesartan and its inactive metabolite, CV-15959, as well as angiotensin I and II, aldosterone, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) activity. The AUC and Cmax of candesartan showed dose-proportional increases in the dose range of 2-16 mg candesartan cilexetil after both single and repeated once-daily tablet intake, indicating linear pharmacokinetics in both younger and elderly healthy subjects. The pharmacokinetics did not change on repeated dosing and, as expected from the half-life of candesartan of approximately 9 h in younger subjects, there was almost no accumulation after repeated once-daily dosing. The time to peak candesartan concentrations after tablet intake was consistently approximately 4 h at all dose levels. Both Cmax and AUC of candesartan were increased after single and repeated once-daily dosing in the elderly compared to younger subjects by approximately 50%. However, no accumulation after repeated once-daily dosing were seen in the elderly. The half-life of candesartan in the elderly (9-12 h) was somewhat longer than in the younger healthy adult volunteers (approximately 9 h) and no gender-related differences in the disposition of candesartan were observed. Serum concentrations of CV-15959 were much lower than candesartan, and reached peak serum concentrations later, about 4-9 h after dose intake. The elimination of CV-15959 was somewhat slower than that of candesartan. Candesartan cilexetil, the prodrug to candesartan, was not measurable in serum. No differences in ACE activity or serum aldosterone concentrations were observed between subjects receiving candesartan cilexetil and placebo tablets. Plasma angiotensin I and II concentrations and PRA were augmented after single doses and further increased after 1 week repeated candesartan cilexetil dosing. Single and repeated doses of candesartan cilexetil were well tolerated in the younger and elderly volunteers. Only mild adverse events were recorded, with 'headache' as the most commonly reported event, and no increase in the number of reported adverse events was observed with higher doses of candesartan cilexetil. No clinically significant changes in respect to vital signs, physical examination, ECG, and clinical laboratory tests were observed.
journal_name
J Hum Hypertensjournal_title
Journal of human hypertensionauthors
Hübner R,Högemann AM,Sunzel M,Riddell JGsubject
Has Abstractpub_date
1997-09-01 00:00:00pages
S19-25eissn
0950-9240issn
1476-5527journal_volume
11 Suppl 2pub_type
临床试验,杂志文章,随机对照试验abstract::The United Kingdom has successfully implemented a salt reduction programme. We carried out a comprehensive analysis of the programme with an aim of providing a step-by-step guide of developing and implementing a national salt reduction strategy, which other countries could follow. The key components include (1) settin...
journal_title:Journal of human hypertension
pub_type: 杂志文章,评审
doi:10.1038/jhh.2013.105
更新日期:2014-06-01 00:00:00
abstract::The African population is considered a high-risk group for the development of hypertension, and identifying risk factors are therefore essential in preventive actions against cardiovascular disease (CVD). Elevated levels of uric acid (UA) are often associated with CVD. Our first aim was to establish possible ethnic di...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2010.1
更新日期:2010-10-01 00:00:00
abstract::Three controlled dietary intervention studies were carried out in 1981-1983 in North Karelia, Finland, to asses the impact of dietary fat intake modification on blood pressure (BP). All these studies involved middle-aged men and women in rural or semirural areas and comprised a baseline period, a six week (or 12 weeks...
journal_title:Journal of human hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1987-12-01 00:00:00
abstract::A total of 78 Chinese patients with clinically uncomplicated non-insulin-dependent diabetes (NIDDM) who had plasma creatinine concentrations of < 150 mumol/l were studied. Antihypertensive treatment was discontinued for at least six weeks prior to measurements of routine biochemistry, proteinuria, plasma atrial natriu...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::To evaluate ethnic differences in cerebral circulation, an index of carotid vascular resistance (RI) was determined by continuous wave Doppler ultrasound. Validation of the index resulted from a significant correlation between RI and carotid vascular resistance obtained from direct measurement of blood pressure and ca...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::The aim of this study was to ascertain the relationship between social network and the appearance of mortality (cardiovascular events (CVEs)) in patients with arterial hypertension (AHT). This is a cohort study of 236 patients with a 9-year follow-up. Measurements included age, sex, blood pressure (BP), diabetes, hype...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2014.116
更新日期:2015-07-01 00:00:00
abstract::Losartan, enalapril and amlodipine reduced the number of premature ventricular contractions (PVCs) in patients with essential hypertension as well as blood pressure. The effect of losartan was the most prominent among the three drugs. ...
journal_title:Journal of human hypertension
pub_type: 临床试验,信件
doi:10.1038/jhh.2008.122
更新日期:2009-04-01 00:00:00
abstract::The purpose of this study is to review the role of dopamine in hypertension and associated conditions. The analysis of literature indicates that present knowledge is mostly based on poor markers and indirect evidence of dopaminergic activity and only few molecular biological data. Alternative markers such as plasma do...
journal_title:Journal of human hypertension
pub_type: 杂志文章,评审
doi:10.1038/sj.jhh.1000870
更新日期:1999-09-01 00:00:00
abstract::Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investiga...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1001601
更新日期:2003-10-01 00:00:00
abstract::There are complications in diagnosing hypertension in children and adolescents due to variation of blood pressure (BP) values to age, gender and height. This study was aimed at assessing whether the performance of BP-to-height ratio (BPHR) can be an effective tool for screening prehypertension and hypertension in Elli...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2017.25
更新日期:2017-09-01 00:00:00
abstract::Blood pressure (BP) is known to vary by time of day and day of year. Studies differ substantially on the magnitude of the effect and there is doubt whether variation is clinically meaningful. We used more than 2 million BP measurements obtained between 1996 and 2004 from Geisinger Clinic primary care patients. General...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2008.44
更新日期:2008-11-01 00:00:00
abstract::Intracranial atherosclerotic stenosis (ICAS) contributes to nearly 50% of stroke in China, especially in patients with hypertension. Urine albumin-to-creatinine ratio (ACR) has been related to stroke and other atherosclerotic cardiovascular diseases. However, there is limited information about the association of ACR a...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/s41371-019-0201-3
更新日期:2019-06-01 00:00:00
abstract::Altitude affects blood pressure (BP) depending on duration and absolute altitude of exposure. Until now changes in BP during exposure to altitude were studied only in Caucasians. It is not known whether BP is affected differently in black and white people in response to altitude. During a 6-day climb on Kilimanjaro, B...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1000468
更新日期:1997-07-01 00:00:00
abstract::Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50-84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 2...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2016.78
更新日期:2017-05-01 00:00:00
abstract::In phaeochromocytoma, sudden hypertensive or arrhythmic episodes are believed to be associated with excessive free catecholamine excretion. However, lack of correlation between blood pressure (BP) and plasma catecholamine levels has been reported. Therefore an attempt was made to assess the sympathovagal balance befor...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Both trandolapril and verapamil are effective and widely used antihypertensive agents. The aim of this study was to estimate the efficacy and tolerability of trandolapril/verapamil (Tr/Ve) combination for blood pressure control and renoprotection. PubMed, EMBASE and Cochrane Library were searched for relevant studies....
journal_title:Journal of human hypertension
pub_type: 杂志文章,meta分析
doi:10.1038/jhh.2010.60
更新日期:2011-03-01 00:00:00
abstract::Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive ...
journal_title:Journal of human hypertension
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.jhh.1002220
更新日期:2007-10-01 00:00:00
abstract::Dopamine is a natriuretic hormone which is synthesised within the kidney. We have previously found that some ethnic groups (e.g. British Caucasians and Thais) show strong positive correlations between 24 h urinary sodium and dopamine outputs. However no such relationship was found in Iranians and black West Africans. ...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:
更新日期:1990-04-01 00:00:00
abstract::This study investigated the period of time that blood pressure (BP) should be measured at home in older patients in order to obtain steady BP values. Thirty-six men and 38 women (> or =60 years) were recruited at one family practice. At one office visit the family physician measured supine, sitting and standing BPs th...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1000517
更新日期:1997-10-01 00:00:00
abstract::We aimed to investigate whether the effect of problematic alcohol drinking on hypertension differed according to metabolic health statuses. Male participants from the fifth Korea National Health and Nutrition Examination Survey were recruited. Problematic alcohol drinkers were designated as subjects with heavy drinkin...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2015.102
更新日期:2016-10-01 00:00:00
abstract::Platelet shape change (PSC) is an early phase of platelet activation that precedes platelet aggregation. This phase of platelet activation is essentially aspirin resistant. PSC was monitored, by measuring the median platelet volume (MPV) using a high resolution channelyser. Angiotensin (Ang) II, added in vitro, caused...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1001102
更新日期:2000-09-01 00:00:00
abstract::Isolated segments (1-2 mm) of small subcutaneous arteries (diameter 0.1-0.9 mm) and veins (0.1-1.0 mm) from patients with hypertension (essential n = 13, renovascular n = 6) and controls (n = 17) were examined. The relaxant responses to the sensory transmitters calcitonin gene-related peptide (CGRP) and substance P, a...
journal_title:Journal of human hypertension
pub_type: 临床试验,杂志文章
doi:10.1038/sj.jhh.1001294
更新日期:2002-01-01 00:00:00
abstract::This work examines the association between hypertension and hypothyroidism in geriatric patients seen at a primary care medical office. One hundred and twenty-two geriatric patients with elevated thyroid stimulating hormone (TSH) levels were selected for the study. An equal number of euthyroid geriatric individuals we...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1000799
更新日期:1999-04-01 00:00:00
abstract::To investigate a possible association between miR-101 and apoptosis of human trophoblast cells mediated by endoplasmic reticulum protein 44 (ERp44) in preeclampsia (PE), we explored the expression of miR-101 in PE placentas (n=30) compared with normotensive pregnant placentas (n=30) and the correlation between miR-101...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2014.35
更新日期:2014-10-01 00:00:00
abstract::The systemic oxidative status in hypertensives disorders of pregnancy (HDP) and its association with endothelial dysfunction is controversial. In the present study, we evaluated systemic plasma levels of oxidative stress markers (TBARS (thiobarbituric acid-reactive substances) and carbonyl) and total antioxidant statu...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/jhh.2012.58
更新日期:2013-06-01 00:00:00
abstract::Within routine clinical practice, white coat hypertension (where blood pressure is persistently higher in the presence of the doctor or nurse but normal outside the medical setting) makes the diagnosis and management of hypertension difficult. There are conflicting data regarding the prevalence and significance of whi...
journal_title:Journal of human hypertension
pub_type: 临床试验,杂志文章
doi:10.1038/sj.jhh.1000924
更新日期:1999-12-01 00:00:00
abstract::New onset of seizures in young adults is frequently related to alcohol withdrawal, toxic exposure, central nervous system trauma and neoplasm. We describe a young soldier presenting to the emergency department with seizures and transient coma. On admission, he had hypertension, marked leukocytosis, hyper-glycaemia, ac...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1001499
更新日期:2003-01-01 00:00:00
abstract::The objective of the study was to determine trends in age-specific blood pressure (BP) distribution and hypertension prevalence in an urban Indian population. In successive hypertension epidemiological studies (1995 and 2002), randomly selected 2212 subjects (1412 men, 797 women) in the first and 1123 subjects (550 me...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:10.1038/sj.jhh.1001588
更新日期:2003-08-01 00:00:00
abstract::There is growing evidence that hypertension, one of the major modifiable risk factors for cardiovascular disease (CVD), is established early in life. Given this, it is important to discover when hypertension first becomes apparent. Further, it is of particular importance to examine the ethnic differences in blood pres...
journal_title:Journal of human hypertension
pub_type: 杂志文章,评审
doi:10.1038/sj.jhh.1001674
更新日期:2004-04-01 00:00:00
abstract::It has been suggested that risks of hypertension and cardiovascular disease begin in utero and that maternal nutrition plays an important role. We have examined the relation between maternal factors and BP in a study of 1,311 children in which physical measurements at 9-11 years of age have been linked to a parental q...
journal_title:Journal of human hypertension
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00