Abstract:
OBJECTIVE:To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS:Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international normalized ratio (INR) was targeted between 2 and 3, monitored every week until four consecutive adequate measures had been obtained, and then monthly. Serious hemorrhagic events were defined by the need for inpatient hospitalization. CYP2C9 genotyping was obtained by PCR-RFLP. RESULTS:The frequencies of CYP2C9*2 and CYP2C9*3 were 0.097 and 0.073, respectively, with genotypic distribution fitting Hardy-Weinberg equilibrium. CYP2C9 genotype was the only clinical feature associated with the risk of severe bleeding (one-sided P = 0.019, Fisher exact method), with an odds ratio of 4.8 (95% confidence interval of 1.4-16.6) for any variant genotype as compared to CYP2C9*1*1. Patients with either CYP2C9*2 or CYP2C9*3 were equally difficult to maintain in the INR target range, showing significantly (one-sided P = 0.038, Mann-Whitney U-test) reduced ratio of adequate INR measures (0.54 +/- 0.2), when compared to CYP2C9*1*1 patients (0.63 +/- 0.2). Patients with CYP2C9*3, but not CYP2C9*2, required significantly (one-sided P = 0.001, Mann-Whitney U-test) lower warfarin maintenance doses (3.1 +/- 1.8 mg) than CYP2C9*1*1 patients (5.3 +/- 2.1 mg). CONCLUSION:Patients with either CYP2C9*2 or CYP2C9*3 show higher risk of over-anticoagulation compared to CYP2C9*1*1 subjects and could benefit from a reduction in the initial warfarin standard dose (e.g., to 2.5 mg/day).
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Lima MV,Ribeiro GS,Mesquita ET,Victer PR,Vianna-Jorge Rdoi
10.1007/s00228-007-0385-2subject
Has Abstractpub_date
2008-01-01 00:00:00pages
9-15issue
1eissn
0031-6970issn
1432-1041journal_volume
64pub_type
杂志文章abstract:PURPOSE:LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor, is indicated for chronic heart failure (HF) and reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization for HF. Following oral administration, LCZ696 provides systemic exposure to valsartan and ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2072-7
更新日期:2016-09-01 00:00:00
abstract:PURPOSE:In this study, the risk factors associated with sodium overcorrection were investigated with an optimal cutoff for baseline serum sodium for use in daily clinical practice. METHODS:Electronic medical records of patients who received tolvaptan for non-hypovolemic hyponatremia were reviewed. Demographic and clin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02848-6
更新日期:2020-05-01 00:00:00
abstract::To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipin...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00315275
更新日期:1993-01-01 00:00:00
abstract::Arginine vasopressin (AVP) is the major physiological regulator of renal water excretion and blood volume. The AVP pathways of V(1a)R-mediated vasoconstriction and V(2)R-induced water retention represent a potentially attractive target of therapy for edematous diseases. Experimental and clinical evidence suggests bene...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-011-1006-7
更新日期:2011-04-01 00:00:00
abstract::Glycerol 50 g infused i.v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00278481
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:Little is known about patient compliance with oral adjuvant chemotherapy. It is estimated to be poor especially in Japan, where it is still unusual for patients to be directly informed of their diagnosis of malignancy. 5-Fluorouracil (5-FU) was measured in hair samples to assess patient exposure to 5-FU, and ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002280050077
更新日期:1996-01-01 00:00:00
abstract::Intensive monitoring of adverse drug reactions (ADR) in infants and preschool children in the paediatric outpatient unit covering the town of Karlovac (150,000 inhabitants) was performed over a period of three months. Data were obtained by physical examination of children and the history given by their parents. In all...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561025
更新日期:1989-01-01 00:00:00
abstract::Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continuous infusion of 0.2 micrograms.kg-1.min-1. Haemodynamic measurements were per...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314795
更新日期:1990-01-01 00:00:00
abstract::The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558162
更新日期:1989-01-01 00:00:00
abstract::We report the first placebo controlled parallel group study of once daily endralazine (5-20 mg) in hypertension uncontrolled by a beta-blocker plus a diuretic. Following a 4-week run-in period 22 patients with a sitting mean arterial pressure (MAP) greater than 110 mm Hg were entered into the study and received either...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00613452
更新日期:1985-01-01 00:00:00
abstract::The antihypertensive effects of urapidil and clonidine have been studied in a double-blind cross-over trial in 11 hypertensive outpatients with mild to moderate hypertension, at rest and during isometric exercise. Urapidil 30 mg b.i.d. significantly decreased the standing diastolic blood pressure (p less than 0.05) an...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00635705
更新日期:1985-01-01 00:00:00
abstract::A cross-over study of kinetics has been undertaken in 12 healthy adults volunteers using two sustained-release theophylline products that allow once a day dosing (Theo-Dur tablets and Dilatrane A.P. bead filled capsules) to compare the i.v. pharmacokinetic profiles when taken with an hyperlipidic meal and a balanced s...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00609431
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. METHODS:Sulfotran...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000168
更新日期:2000-09-01 00:00:00
abstract:PURPOSE:The role of pharmacogenomics, clinical and demographic parameters in pharmacokinetic predictions was evaluated in patients receiving mycophenolic acid (MPA). METHODS:A cohort study design of patients with glomerulonephritis secondary to lupus nephritis and anti-neutrophil cytoplasmic antibody (ANCA) vasculitis...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0846-x
更新日期:2010-11-01 00:00:00
abstract::The inhibitory action of azelastine hydrochloride (Azeptin) on the respiratory burst in peripheral polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM) has been studied. Azeptin in vitro suppressed chemiluminescence and superoxide (O2-) generation by human PMN in a dose- and time-dependent manne...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00194963
更新日期:1994-01-01 00:00:00
abstract:OBJECTIVE:Losartan was given to subjects with known phenotypes of the polymorphic enzymes CYP2D6 and CYP2C19 to study any possible influence on the metabolism of the drug. METHODS:Plasma concentrations of losartan and E-3174 were studied after oral intake of 50 mg losartan in 24 healthy, male, Swedish Caucasian subjec...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050629
更新日期:1999-06-01 00:00:00
abstract:CASE REPORTS:Two women treated with agalsidase alpha for Fabry disease developed severe heart dysfunctions a few months after the beginning of enzyme replacement therapy (ERT). An adverse effect caused by the treatment was suspected; therefore we informed the French pharmacovigilance authorities about these two events....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0460-8
更新日期:2008-06-01 00:00:00
abstract::The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00637599
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:To determine whether two of the major operational stressors associated with military missions in Afghanistan: dry heat and long durations of soldier patrol (SP), alter the pharmacokinetics of ibuprofen. METHODS:Thirteen healthy and physically fit participants (19-32 years) were randomized to a four-arm crossov...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00228-012-1307-5
更新日期:2013-01-01 00:00:00
abstract::Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was repl...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00202174
更新日期:1995-01-01 00:00:00
abstract::Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-liv...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00616416
更新日期:1975-01-01 00:00:00
abstract:BACKGROUND:Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-020-03005-9
更新日期:2020-10-06 00:00:00
abstract::The plasma pharmacokinetics of adriamycin has been studied in 21 cancer patients (31-85 years old) without liver tumours after short (3.00 min) and prolonged (45 min-16 h) i.v. infusions. The area under the plasma concentration-time curve and the maximum plasma concentration compensated for dose variation showed a mor...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00609693
更新日期:1985-01-01 00:00:00
abstract::The metabolism of hydralazine in a group of slow acetylator patients with the drug-induced lupus syndrome was compared with the metabolism in asymptomatic control subjects. There were no toxicologically significant difference in metabolite excretion between the groups which reached statistical significance, although t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00556891
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. METHODS:Pertinent randomized controlled trials were selected through a search of Pubmed, Embas...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00228-011-1008-5
更新日期:2011-08-01 00:00:00
abstract:PURPOSE:Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-017-2388-y
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVE:The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain. METHODS:Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving birth who requested pain...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0955-0
更新日期:2005-08-01 00:00:00
abstract::The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pl...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00548772
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVE:The present study was undertaken to investigate the possible effects of various agents on thiopurine methyltransferase (TPMT) activity in red blood cells (RBCs) from patients with chronic inflammatory bowel disease (IBD). METHODS:In three groups of patients with very high, normal and intermediate TPMT activi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0950-5
更新日期:2005-07-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate whether there is an association between anticholinergic burden and mortality or rehospitalization in older adults discharged from hospital. METHODS:Prospective multicenter cohort study carried out with patients aged 65 and older discharged from seven acute care hospi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-017-2312-5
更新日期:2017-11-01 00:00:00