Abstract:
OBJECTIVE:NXY-059 is a nitrone-based, free-radical trapping agent being developed for the treatment of acute ischaemic stroke. Elimination of NXY-059 is primarily renal. The objective of the study was to investigate the pharmacokinetics of NXY-059 in subjects with renal impairment. METHODS:Twenty-four subjects with a glomerular filtration rate (GFR) ranging from 19 ml/min to 100 ml/min received NXY-059 intravenously over a 24-h period. Drug in plasma and urine was measured for 72 h. One-hour loading infusion rates were proportional to body weight, while maintenance infusion rates were proportional to GFR. Target plasma levels were 60 micro mol/l for subjects with mild (GFR 50-100 ml/min) and moderate (GFR 30-49 ml/min) renal impairment, and 30 micro mol/l for subjects with severe renal impairment (GFR <30 ml/min). GFR was measured as sinistrin clearance. RESULTS:The data indicated no tolerability or safety concerns with NXY-059. The half-life, which normally is approximately 2-4 h, was in the order of 10-12 h in subjects with moderate and severe renal impairment. The distribution parameters steady-state volume of distribution (V(ss)) and unbound fraction in plasma at 13-15 l and 0.53-0.58, respectively, were virtually the same as previously observed in healthy subjects. Plasma clearance of NXY-059, which ranged from 9 ml/min to 76 ml/min, was directly proportional to kidney function (GFR) with no discernible contribution by non-renal clearance. The correlation coefficient squared (r(2)) was 0.93, both when the renal function parameter was GFR and when it was creatinine clearance estimated from serum creatinine, age, weight and sex. CONCLUSION:Non-renal elimination of NXY-059 appeared to be insignificant even in subjects with low renal capacity. Patients with renal impairment should have their dose of NXY-059 adjusted for renal function, conveniently assessed from serum creatinine.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Strid S,Borgå O,Edenius C,Jostell KG,Odergren T,Weil Adoi
10.1007/s00228-002-0478-xsubject
Has Abstractpub_date
2002-09-01 00:00:00pages
409-15issue
6eissn
0031-6970issn
1432-1041journal_volume
58pub_type
临床试验,杂志文章abstract::The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then de...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315284
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lo...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0847-9
更新日期:2010-10-01 00:00:00
abstract::The effect of menstrual cycle on the pharmacokinetics of theophylline has been studied in 9 female asthmatic patients. At three different times during the cycle (first, tenth and twentieth days) each subject received an i.v. infusion of 240 mg theophylline. Significant changes were found in the kinetics of theophyllin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02657059
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:To investigate associations between antidepressant use patterns and risk of fatal and non-fatal suicidal behaviours in older adults who initiated antidepressant therapy. METHOD:A national population-based cohort study conducted among Swedish residents aged ≥ 75 years who initiated antidepressant treatment. Pat...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-017-2360-x
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVE:To assess the effect of an intervention on general practitioners' (GPs) knowledge about the diagnosis and treatment of asthma, including the prescribing of anti-asthmatic drugs, and asthmatic patients' knowledge about their disease. METHODS:The study took place in the south-west region of Stockholm County. I...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050361
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:Xanthine oxidase (XO) is one of the two interconvertible forms of xanthine oxidoreductase and well-studied for its role in purine catabolism and that of other purine analogues, drugs especially. Our study investigated the incidence of polymorphism in phenotypes along with the influence of gender and age on e...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1852-9
更新日期:2015-06-01 00:00:00
abstract::The pharmacokinetics of intravenous chloramphenicol has been studied in 42 patients with liver disease and in 8 controls. The half-life of chloramphenicol (t 1/2) was increased in the various liver disorders, the metabolic clearance rate (MCR) and apparent volume of distribution (Vd) were decreased and the area under ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542103
更新日期:1981-01-01 00:00:00
abstract:PURPOSE:The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS:Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-016-2133-y
更新日期:2017-01-01 00:00:00
abstract::Although the aminopyrine breath test has received much attention, the question has not yet been settled whether pharmacological or tracer doses of the drug should be used. Nine volunteers were given 14C-aminopyrine 9 mg/kg or a tracer amount, in a randomized sequence and according to a crossover design. The specific a...
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/BF00609866
更新日期:1977-11-14 00:00:00
abstract:PURPOSE:Intravenous (IV) magnesium sulfate (MgSO4) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. METHODS:To explore the pharmacokinetics (PK) of IV MgSO4 in this population, we collected retrospect...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2165-3
更新日期:2017-03-01 00:00:00
abstract:OBJECTIVES:To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. METHODS:Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-011-1110-8
更新日期:2012-02-01 00:00:00
abstract::Verapamil, 0.1 mg/kg body wt, was injected i.v. over 2 minutes in 8 subjectively healthy middle-aged men, followed by a continuous infusion of 0.007 mg/kg body wt per minute. Prior to the injection several of the subjects had raised pulmonary or systemic arterial pressures. At rest, the central pressures increased sli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00562656
更新日期:1975-06-13 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:AIM:Our aim was to characterize utilization patterns for drugs used to treat attention deficit/hyperactivity disorder (ADHD) on the level of the individual patient among Danish users, focusing on treatment duration, doses used, and concurrent use of ADHD and non-ADHD drugs. METHODS:Using the Danish Registry of Medicin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1344-0
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVE:In elderly patients, both falls and impaired memory are considerable medical problems. Hypnotics, which are frequently administered to this patient group for the treatment of insomnia, should ideally not impair equilibrium or memory functions. This double-blind, randomised, four-way, cross-over study investig...
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/s00228-003-0591-5
更新日期:2003-07-01 00:00:00
abstract::Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or beta-receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543335
更新日期:1985-01-01 00:00:00
abstract::Oral and sublingual isoxsuprine 20 mg were compared with placebo in double blind randomised cross over trial in 7 patients with Raynaud's phenomenon. Skin thermography, plethysmography of the finger tips and direct temperature measurements showed that sublingual isoxsuprine was slightly but consistently superior to th...
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/BF00615400
更新日期:1981-01-01 00:00:00
abstract::This study examined dosage prescribing patterns and steady-state oxipurinol plasma concentrations in 66 patients receiving chronic allopurinol therapy. Most patients (65%) were taking 300 mg allopurinol daily, although renal impairment was common. Using published guidelines, it was estimated that 35% of patients were ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315424
更新日期:1990-01-01 00:00:00
abstract::The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volum...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00716385
更新日期:1978-12-18 00:00:00
abstract::Pharmacokinetic and pharmacodynamic properties of a new controlled-release (CR) formulation of metoprolol have been compared with those of atenolol. Metoprolol CR (100 mg and 200 mg), atenolol (50 mg and 100 mg) and placebo were each given once daily for four days in a double-blind, cross-over study to ten healthy men...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00578408
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:This study was performed to determine the oral pharmacokinetics (PK) of EV-077 and its effects on pharmacodynamic (PD) markers. EV-077 blocks prostanoid-induced and isoprostane-induced cellular activation, and is in development for the treatment of vascular inflammation and associated complications of type-2 di...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-012-1348-9
更新日期:2013-03-01 00:00:00
abstract:PURPOSE:Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine wh...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-015-1934-8
更新日期:2015-12-01 00:00:00
abstract::Bay m 1099 is a newly developed inhibitor of intestinal alpha-glucosidase. Its ability to lower postprandial plasma glucose, serum insulin and C-peptide levels in Type II diabetics has been investigated. Fifteen obese Type II diabetic patients with inadequate metabolic control during sulphonylurea treatment received a...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00607953
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:To determine the effects of itraconazole, a potent inhibitor of CYP3A4, on the pharmacokinetics of cerivastatin, a competitive 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. METHODS:A randomized, double-blind, cross-over study design with two phases, which were separated by a washout pe...
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/s002280050566
更新日期:1999-01-01 00:00:00
abstract:AIM:Mizoribine (MZR) is an immunosuppressant for the prevention of allograft rejection in Asian countries, but the great variability in pharmacokinetics (PK) limits its clinical use. This study was to explore genetic and clinical factors that affect the MZR PK process. METHODS:Blood samples and clinical data were coll...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02936-7
更新日期:2021-01-01 00:00:00
abstract::The maternofetal transfer of the beta 1-selective adrenergic antagonist celiprolol has been studied in four hypertensive pregnant women. Fetal plasma concentrations were about 25-50% of the levels found on the maternal side. There was no significant difference between the plasma concentrations of the two enantiomers i...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00316477
更新日期:1993-01-01 00:00:00
abstract::A double blind, placebo-controlled study of the ventilatory effects of three new beta 1-selective adrenoceptor blockers was carried out in eight asthmatic patients. Measurements were performed before and 2, 3 and 4 h after ingestion of a single oral dose of placebo, atenolol 100 mg, metoprolol 100 mg or acebutolol 400...
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/BF00542093
更新日期:1981-01-01 00:00:00
abstract:OBJECTIVE:To describe the quantitative and qualitative changes in the utilization of oral antihyperglycemic drugs (OAHDs) between 1998 and 2004 and to analyze patients' adherence to OAHD therapy. METHODS:We conducted a retrospective analysis of the electronic database of the Hungarian National Health Fund Administrati...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0031-9
更新日期:2005-12-01 00:00:00
abstract::Nine healthy adults were administered indocyanine green (ICG) 0.5 mg.kg-1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679780
更新日期:1989-01-01 00:00:00
abstract::A survey among hospital staff physicians was conducted in order to evaluate their attitudes towards systemic antimicrobial agents. Direct questions about the value of different agents and choice within pairs of antimicrobial drugs, stating the reasons for the preference, were included in the questionnaire used. Gentam...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609876
更新日期:1979-03-26 00:00:00