Abstract：
OBJECTIVE:The purpose of this study was to investigate in healthy male subjects the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of clazosentan, an intravenous endothelin receptor antagonist. METHODS:Clazosentan was infused at doses of 3-60 mg/h for 3 h, 60 mg/h for 6 h and at 30 mg/h for 12 h. Each dose was given to a separate group of subjects, six of whom received clazosentan and two placebo. Vital signs, ECG, adverse events, and clinical laboratory variables were monitored to assess tolerability. Blood and urine samples were collected frequently for pharmacokinetic and pharmacodynamic determinations. RESULTS:Infusion of clazosentan up to doses of 30 mg/h for 3 h was well tolerated. A dose of 60 mg/h and longer infusions were less well tolerated and three subjects did not complete the 12-h infusion of 30 mg/h due to adverse events. Headache was the most commonly reported adverse event followed by nausea, vomiting, and nasal congestion. The pharmacokinetics of clazosentan were dose proportional in the dose range investigated. Values (mean and 95% confidence intervals) for clearance and volume of distribution at a dose of 10 mg/h for 3 h were 42.2 (36.6, 48.7) l/h and 32.4 (27.0, 38.8) l, respectively. Both variables were independent of dose. The elimination of clazosentan was characterized by a very rapid disposition phase with a half-life of 6-10 min. Compared to baseline, endothelin-1 concentrations increased approximately 2-fold after infusion of clazosentan but no dose-dependent relationship could be discerned for this effect. CONCLUSION:The observed tolerability, pharmacokinetic, and pharmacodynamic profile warrant further clinical development of clazosentan at lower doses.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
van Giersbergen PL,Dingemanse Jdoi
10.1007/s00228-006-0117-zsubject
Has Abstractpub_date
2007-02-01 00:00:00pages
151-8issue
2eissn
0031-6970issn
1432-1041journal_volume
63pub_type
杂志文章,随机对照试验abstract：:The acute effect of a single oral dose of isradipine 5 mg on blood pressure, renal haemodynamics, electrolyte excretion and plasma renin activity was studied in 10 healthy males. Isradipine did not produce a significant change in systolic or diastolic blood pressure, and glomerular filtration rate, renal plasma flow, ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00315405
更新日期：1990-01-01 00:00:00
abstract：:The effect of AS-4370 on gastric emptying was investigated in healthy adults using 99mTc-DTPA. Single doses of AS-4370 2.5, 5 or 10 mg or placebo were administered to 12 subjects in a controlled, double-blind, cross-over study. Tests were performed twice weekly in each subject. Thirty min after administration of test ...
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/BF00314963
更新日期：1991-01-01 00:00:00
abstract：OBJECTIVE:This work aimed at building a population pharmacokinetic (PK) model for lamivudine (LMV), stavudine (STV) and zidovudine (ZDV), estimating their inter and intraindividual PK variability and investigating the influence of different covariates. METHODS:Population PK of LMV, STV and ZDV was separately evaluated...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1007/s00228-007-0337-x
更新日期：2007-11-01 00:00:00
abstract：OBJECTIVE:To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism. METHODS:CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures. RESULTS:The frequency f...
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/s002280100264
更新日期：2001-04-01 00:00:00
abstract：:Plasma concentrations of metoprolol, propranolol oxprenolol, acebutolol and its metabolite diacetolol were measured after single oral doses in young health volunteers. In order to assessed the inter- and intra-subject variability the following pharmacokinetic parameters were compared: AUC0(24), Cmax, tmax and t 1/2. T...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF01061375
更新日期：1982-01-01 00:00:00
abstract：:We have given 12 healthy subjects the H1-antihistamine ebastine (20 mg) or placebo in a double-blind, crossover study for one week each. The subjects were tested for drug effects on Day 6 of each period, and for interactions of ebastine with ethanol (0.8 g.kg-1) on Day 7. On both days, the testing runs were done at ba...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF01740667
更新日期：1992-01-01 00:00:00
abstract：PURPOSE:this study aimed to investigate the effect of antivirals ritonavir and lopinavir/ritonavir on the pharmacokinetics and pharmacodynamics of oral oxycodone, a widely used opioid receptor agonist used in the treatment of moderate to severe pain. METHODS:a randomized crossover study design with three phases at int...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-010-0879-1
更新日期：2010-10-01 00:00:00
abstract：OBJECTIVE:The effect of age on the pharmacokinetics and pharmacodynamics of prazosin (alpha 1 adrenoceptor blocker) was studied in 20 healthy volunteers. PATIENTS:Ten elderly (61-81 y) and ten young (23-28 y) subjects were studied. All subjects received 1 mg of prazosin orally in a fasting state. Serial blood samples ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050067
更新日期：1996-01-01 00:00:00
abstract：:In this paper an alternative approach to nonlinear pharmacokinetics modelling has been developed from first principles. This "Unsteady Model" is able to describe the situation whereby one or more independent drugs and their metabolites compete for free attachment sites in liver, tissue, red blood cells etc. The Unstea...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00615410
更新日期：1981-01-01 00:00:00
abstract：PURPOSE:A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS:An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0535-1
更新日期：2008-12-01 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：OBJECTIVE:Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA). METHODS:In an open pro...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0153-8
更新日期：2006-09-01 00:00:00
abstract：:In a cross-over study of six healthy male volunteers, 500 mg theophylline was administered either as plain tablets or in a sustained release preparation. On each occasion 2 g of non-enteric coated sulphasalazine was administered simultaneously as the time of appearance of sulphapyridine, the product of hydrolysis, in ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00265979
更新日期：1990-01-01 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 investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters. METHODS:The study had an open, randomised, four-way cross-over design. Desmopressin was administered o...
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/s00228-004-0781-9
更新日期：2004-08-01 00:00:00
abstract：:The effect of the aminoglycosides amikacin, gentamicin, netilmicin sisomicin and tobramycin on the proximal tubule of the human kidney was investigated in 78 healthy subjects. Fifteen adults were each given gentamicin, sisomicin or tobramycin 3 mg/kg bodyweight, 10 subjects received netilmicin 3 mg/kg or amikacin 15 m...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00609758
更新日期：1978-05-17 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：:The possible interaction between cetirizine 2 HCl and alcohol was studied in a double-blind, cross-over trial in 36 healthy volunteers. The performance of each volunteer was tested with a battery of five objective psychometric tests, and their subjective feelings were evaluated by visual analogue scales, and by extens...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00615227
更新日期：1988-01-01 00:00:00
abstract：:Ten normal adult tobacco smokers and 10 nonsmoking volunteers 20-31 years of age were the subjects of this study. The tobacco smokers all had a history of daily tobacco smoking. They were asked to stop smoking for 12 hours prior to testing. The Hoffmann (H) reflex and its recovery cycle were measured on different days...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00196110
更新日期：1994-01-01 00:00:00
abstract：:The frequency distribution of the 8-h urinary ratio of log metoprolol/alpha-hydroxymetoprolol was assessed in 65 healthy, unrelated Jordanian volunteers. There was no apparent bimodality in the frequency distribution of this ratio among the subjects studied. The frequency of the poor metabolizer phenotype of metoprolo...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00191160
更新日期：1994-01-01 00:00:00
abstract：:Seventeen patients underwent tonsillectomy 55-120 min after receiving oral phenoxymethylpenicillin 12.5 mg/kg bodyweight. The penicillin concentration in serum and tonsillar tissue in each patient was determined by a microbial assay. In 9 patients with tonsillar hyperplasia, but with no prior history of tonsillitis, t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315423
更新日期：1990-01-01 00:00:00
abstract：:The four sulphonamides studied--furosemide, tolbutamide, sulfafurazole and sulfonamidochlorobenzoic acid--bind to human albumin at the same sites but with decreasing affinity. These sites are also common to other drugs, namely acenocoumarin, chlorophenoxyisobutyric acid, phenylbutazone and warfarin. In plasma, the fou...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00609473
更新日期：1976-06-15 00:00:00
abstract：PURPOSE:This study aims to compare the prevalence of potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs) using several screening tools in an Irish community-dwelling older cohort, to assess if the prevalence changes over time and to determine factors associated with any change. METHOD...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1815-1
更新日期：2015-04-01 00:00:00
abstract：:The blood level versus time curve for unchanged cimetidine after a 200 mg oral dose has been determined in 20 apparently healthy subjects, ranging from 22 to 84 years of age. A significant relationship between the area under the curve (AUC) and age was found (r = 0.81; P less than 0.001). The peak concentrations of ci...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00618514
更新日期：1979-05-21 00:00:00
abstract：:Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast can...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00562896
更新日期：1977-01-03 00:00:00
abstract：:The effects of an oral dose of atropine (0.03 mg/kg body weight) and an IM (0.02 mg/kg) dose on the heart rate and salivary flow in seven healthy adult volunteers were compared to see whether the oral dose was sufficient to inhibit vagal reflexes of the heart. Atropine concentrations in plasma were determined by an M2...
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/BF00192357
更新日期：1995-01-01 00:00:00
abstract：OBJECTIVE:The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). METHODS:In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0941-6
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:Drug-related problems (DRPs) are common in paediatric pharmacotherapy, but few studies describe them from the parents' perspective. In the present survey, we have investigated the lifetime prevalence and type of DRPs in children in Finland. METHODS:This was a population-based survey of a random sample of 6,000...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-012-1426-z
更新日期：2013-04-01 00:00:00
abstract：PURPOSE:This exploratory study was aimed at elucidating the pharmacogenetics of regulatory nuclear receptors (PXR, CAR, RXRα and HNF4α) and their implications on docetaxel pharmacokinetics and pharmacodynamics in local Chinese nasopharyngeal cancer patients. METHODS:A total of 59 single nucleotide polymorphisms (SNPs)...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-013-1596-3
更新日期：2014-02-01 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
